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231 results on '"da silva, AG"'

1. Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Author: Brauer, M, Roth, GA, Aravkin, AY, Zheng, P, Abate, KH, Abate, YH, Abbafati, C, Abbasgholizadeh, R, Abbasi, MA, Abbasian, M, Abbasifard, M, Abbasi-Kangevari, M, Abd ElHafeez, S, Abd-Elsalam, S, Abdi, P, Abdollahi, M, Abdoun, M, Abdulah, DM, Abdullahi, A, Abebe, M, Abedi, A, Abegaz, TM, Abeldaño Zuñiga, RA, Abiodun, O, Abiso, TL, Aboagye, RG, Abolhassani, H, Abouzid, M, Aboye, GB, Abreu, LG, Abualruz, H, Abubakar, B, Abu-Gharbieh, E, Abukhadijah, HJJ, Aburuz, S, Abu-Zaid, A, Adane, MM, Addo, IY, Addolorato, G, Adedoyin, RA, Adekanmbi, V, Aden, B, Adetunji, JB, Adeyeoluwa, TE, Adha, R, Adibi, A, Adnani, QES, Adzigbli, LA, Afolabi, AA, Afolabi, RF, Afshin, A, Afyouni, S, Afzal, MS, Afzal, S, Agampodi, SB, Agbozo, F, Aghamiri, S, Agodi, A, Agrawal, A, Agyemang-Duah, W, Ahinkorah, BO, Ahmad, A, Ahmad, D, Ahmad, F, Ahmad, N, Ahmad, S, Ahmad, T, Ahmed, A, Ahmed, LA, Ahmed, MB, Ahmed, S, Ahmed, SA, Ajami, M, Akalu, GT, Akara, EM, Akbarialiabad, H, Akhlaghi, S, Akinosoglou, K, Akinyemiju, T, Akkaif, MA, Akkala, S, Akombi-Inyang, B, Al Awaidy, S, Al Hasan, SM, Alahdab, F, AL-Ahdal, TMA, Alalalmeh, SO, Alalwan, TA, Al-Aly, Z, Alam, K, Alam, N, Alanezi, FM, Alanzi, TM, Albakri, A, AlBataineh, MT, Aldhaleei, WA, Aldridge, RW, Alemayohu, MA, Alemu, YM, Al-Fatly, B, Al-Gheethi, AAS, Al-Habbal, K, Alhabib, KF, Alhassan, RK, Ali, A, Ali, BA, Ali, I, Ali, L, Ali, MU, Ali, R, Ali, SSS, Ali, W, Alicandro, G, Alif, SM, Aljunid, SM, Alla, F, Al-Marwani, S, Al-Mekhlafi, HM, Almustanyir, S, Alomari, MA, Alonso, J, Alqahtani, JS, Alqutaibi, AY, Al-Raddadi, RM, Alrawashdeh, A, Al-Rifai, RH, Alrousan, SM, Al-Sabah, SK, Alshahrani, NZ, Altaany, Z, Altaf, A, Al-Tawfiq, JA, Altirkawi, KA, Aluh, DO, Alvis-Guzman, N, Alvis-Zakzuk, NJ, Alwafi, H, Al-Wardat, MS, Al-Worafi, YM, Aly, H, Aly, S, Alzoubi, KH, Al-Zyoud, W, Amaechi, UA, Aman Mohammadi, M, Amani, R, Amiri, S, Amirzade-Iranaq, MH, Ammirati, E, Amu, H, Amugsi, DA, Amusa, GA, Ancuceanu, R, Anderlini, D, Anderson, JA, Andrade, PP, Andrei, CL, Andrei, T, Anenberg, SC, Angappan, D, Angus, C, Anil, A, Anil, S, Anjum, A, Anoushiravani, A, Antonazzo, IC, Antony, CM, Antriyandarti, E, Anuoluwa, BS, Anvari, D, Anvari, S, Anwar, S, Anwar, SL, Anwer, R, Anyabolo, EE, Anyasodor, AE, Apostol, GLC, Arabloo, J, Arabzadeh Bahri, R, Arafat, M, Areda, D, Aregawi, BB, Aremu, A, Armocida, B, Arndt, MB, Ärnlöv, J, Arooj, M, Artamonov, AA, Artanti, KD, Aruleba, IT, Arumugam, A, Asbeutah, AM, Asgary, S, Asgedom, AA, Ashbaugh, C, Ashemo, MY, Ashraf, T, Askarinejad, A, Assmus, M, Astell-Burt, T, Athar, M, Athari, SS, Atorkey, P, Atreya, A, Aujayeb, A, Ausloos, M, Avila-Burgos, L, Awoke, AA, Ayala Quintanilla, BP, Ayatollahi, H, Ayestas Portugal, C, Ayuso-Mateos, JL, Azadnajafabad, S, Azevedo, RMS, Azhar, GS, Azizi, H, Azzam, AY, Backhaus, IL, Badar, M, Badiye, AD, Bagga, A, Baghdadi, S, Bagheri, N, Bagherieh, S, Bahrami Taghanaki, P, Bai, R, Baig, AA, Baker, JL, Bakkannavar, SM, Balasubramanian, M, Baltatu, OC, Bam, K, Bandyopadhyay, S, Banik, B, Banik, PC, Banke-Thomas, A, Bansal, H, Barchitta, M, Bardhan, M, Bardideh, E, Barker-Collo, SL, Bärnighausen, TW, Barone-Adesi, F, Barqawi, HJ, Barrero, LH, Barrow, A, Barteit, S, Basharat, Z, Basiru, A, Basso, JD, Bastan, M-M, Basu, S, Batchu, S, Batra, K, Batra, R, Baune, BT, Bayati, M, Bayileyegn, NS, Beaney, T, Behnoush, AH, Beiranvand, M, Béjot, Y, Bekele, A, Belgaumi, UI, Bell, AW, Bell, ML, Bello, MB, Bello, OO, Belo, L, Beloukas, A, Bendak, S, Bennett, DA, Bennitt, FB, Bensenor, IM, Benzian, H, Beran, A, Berezvai, Z, Bernabe, E, Bernstein, RS, Bettencourt, PJG, Bhagavathula, AS, Bhala, N, Bhandari, D, Bhardwaj, N, Bhardwaj, P, Bhaskar, S, Bhat, AN, Bhat, V, Bhatti, GK, Bhatti, JS, Bhatti, MS, Bhatti, R, Bhuiyan, MA, Bhutta, ZA, Bikbov, B, Bishai, JD, Bisignano, C, Biswas, A, Biswas, B, Biswas, RK, Bjørge, T, Boachie, MK, Boakye, H, Bockarie, MJ, Bodolica, V, Bodunrin, AO, Bogale, EK, Bolla, SR, Boloor, A, Bonakdar Hashemi, M, Boppana, SH, Bora Basara, B, Borhany, H, Botero Carvajal, A, Bouaoud, S, Boufous, S, Bourne, R, Boxe, C, Braithwaite, D, Brant, LC, Brar, A, Breitborde, NJK, Breitner, S, Brenner, H, Briko, AN, Britton, G, Brown, CS, Browne, AJ, Brunoni, AR, Bryazka, D, Bulamu, NB, Bulto, LN, Buonsenso, D, Burkart, K, Burns, RA, Busse, R, Bustanji, Y, Butt, NS, Butt, ZA, Caetano dos Santos, FL, Cagney, J, Cahuana-Hurtado, L, Calina, D, Cámera, LA, Campos, LA, Campos-Nonato, IR, Cao, C, Cao, F, Cao, Y, Capodici, A, Cárdenas, R, Carr, S, Carreras, G, Carrero, JJ, Carugno, A, Carvalho, F, Carvalho, M, Castaldelli-Maia, JM, Castañeda-Orjuela, CA, Castelpietra, G, Catalá-López, F, Catapano, AL, Cattaruzza, MS, Caye, A, Cederroth, CR, Cegolon, L, Cenderadewi, M, Cercy, KM, Cerin, E, Chadwick, J, Chakraborty, C, Chakraborty, PA, Chakraborty, S, Chan, JSK, Chan, RNC, Chandan, JS, Chandika, RM, Chaturvedi, P, Chen, A-T, Chen, CS, Chen, H, Chen, MX, Chen, M, Chen, S, Cheng, C-Y, Cheng, ETW, Cherbuin, N, Chi, G, Chichagi, F, Chimed-Ochir, O, Chimoriya, R, Ching, PR, Chirinos-Caceres, JL, Chitheer, A, Cho, WCS, Chong, B, Chopra, H, Chowdhury, R, Christopher, DJ, Chu, D-T, Chukwu, IS, Chung, E, Chung, S-C, Chutiyami, M, Cioffi, I, Cogen, RM, Cohen, AJ, Columbus, A, Conde, J, Corlateanu, A, Cortese, S, Cortesi, PA, Costa, VM, Costanzo, S, Criqui, MH, Cruz, JA, Cruz-Martins, N, Culbreth, GT, da Silva, AG, Dadras, O, Dai, X, Dai, Z, Daikwo, PU, Dalli, LL, Damiani, G, D'Amico, E, D'Anna, L, Darwesh, AM, Das, JK, Das, S, Dash, NR, Dashti, M, Dávila-Cervantes, CA, Davis Weaver, N, Davitoiu, DV, De la Hoz, FP, de la Torre-Luque, A, De Leo, D, Debopadhaya, S, Degenhardt, L, Del Bo', C, Delgado-Enciso, I, Delgado-Saborit, JM, Demoze, CK, Denova-Gutiérrez, E, Dervenis, N, Dervišević, E, Desai, HD, Desai, R, Devanbu, VGC, Dewan, SMR, Dhali, A, Dhama, K, Dhane, AS, Dhimal, ML, Dhimal, M, Dhingra, S, Dhulipala, VR, Dhungana, RR, Dias da Silva, D, Diaz, D, Diaz, LA, Diaz, MJ, Dima, A, Ding, DD, Dinu, M, Djalalinia, S, Do, TC, Do, THP, do Prado, CB, Dodangeh, M, Dohare, S, Dokova, KG, Dong, W, Dongarwar, D, D'Oria, M, Dorostkar, F, Dorsey, ER, Doshi, R, Doshmangir, L, Dowou, RK, Driscoll, TR, Dsouza, AC, Dsouza, HL, Dumith, SC, Duncan, BB, Duraes, AR, Duraisamy, S, Dushpanova, A, Dzianach, PA, Dziedzic, AM, Ebrahimi, A, Echieh, CP, Ed-Dra, A, Edinur, HA, Edvardsson, D, Edvardsson, K, Efendi, F, Eftekharimehrabad, A, Eini, E, Ekholuenetale, M, Ekundayo, TC, El Arab, RA, El Sayed Zaki, M, El-Dahiyat, F, Elemam, NM, Elgar, FJ, ElGohary, GMT, Elhabashy, HR, Elhadi, M, Elmehrath, AO, Elmeligy, OAA, Elshaer, M, Elsohaby, I, Emeto, TI, Esfandiari, N, Eshrati, B, Eslami, M, Esmaeili, SV, Estep, K, Etaee, F, Fabin, N, Fagbamigbe, AF, Fagbule, OF, Fahimi, S, Falzone, L, Fareed, M, Farinha, CSES, Faris, MEM, Faris, PS, Faro, A, Fasina, FO, Fatehizadeh, A, Fauk, NK, Fazylov, T, Feigin, VL, Feng, X, Fereshtehnejad, S-M, Feroze, AH, Ferrara, P, Ferrari, AJ, Ferreira, N, Fetensa, G, Feyisa, BR, Filip, I, Fischer, F, Fitriana, I, Flavel, J, Flohr, C, Flood, D, Flor, LS, Foigt, NA, Folayan, MO, Force, LM, Fortuna, D, Foschi, M, Franklin, RC, Freitas, A, Friedman, SD, Fux, B, G, S, Gaal, PA, Gaihre, S, Gajdács, M, Galali, Y, Gallus, S, Gandhi, AP, Ganesan, B, Ganiyani, MA, Garcia, V, Gardner, WM, Garg, RK, Gautam, RK, Gebi, TG, Gebregergis, MW, Gebrehiwot, M, Gebremariam, TBB, Gebremeskel, TG, Gerema, U, Getacher, L, Getahun, GKA, Getie, M, Ghadirian, F, Ghafarian, S, Ghaffari Jolfayi, A, Ghailan, KY, Ghajar, A, Ghasemi, M, Ghasempour Dabaghi, G, Ghasemzadeh, A, Ghassemi, F, Ghazy, RM, Gholami, A, Gholamrezanezhad, A, Gholizadeh, N, Ghorbani, M, Gil, AU, Gil, GF, Gilbertson, NM, Gill, PS, Gill, TK, Gindaba, EZ, Girmay, A, Glasbey, JC, Gnedovskaya, EV, Göbölös, L, Godinho, MA, Goel, A, Golechha, M, Goleij, P, Golinelli, D, Gomes, NGM, Gopalani, SV, Gorini, G, Goudarzi, H, Goulart, AC, Gouravani, M, Goyal, A, Graham, SM, Grivna, M, Grosso, G, Guan, S-Y, Guarducci, G, Gubari, MIM, Guha, A, Guicciardi, S, Gulati, S, Gulisashvili, D, Gunawardane, DA, Guo, C, Gupta, AK, Gupta, B, Gupta, M, Gupta, R, Gupta, RD, Gupta, S, Gupta, VB, Gupta, VK, Habibzadeh, F, Habibzadeh, P, Hadaro, TS, Hadian, Z, Haep, N, Haghi-Aminjan, H, Haghmorad, D, Hagins, H, Haile, D, Hailu, A, Hajj Ali, A, Halboub, ES, Halimi, A, Hall, BJ, Haller, S, Halwani, R, Hamadeh, RR, Hamdy, NM, Hameed, S, Hamidi, S, Hammoud, A, Hanif, A, Hanifi, N, Haq, ZA, Haque, MR, Harapan, H, Hargono, A, Haro, JM, Hasaballah, AI, Hasan, I, Hasan, MJ, Hasan, SMM, Hasani, H, Hasanian, M, Hashmeh, N, Hasnain, MS, Hassan, A, Hassan, I, Hassan Zadeh Tabatabaei, MS, Hassani, S, Hassanipour, S, Hassankhani, H, Haubold, J, Havmoeller, RJ, Hay, SI, Hebert, JJ, Hegazi, OE, Hegena, TY, Heidari, G, Heidari, M, Helfer, B, Hemmati, M, Henson, CA, Herbert, ME, Herteliu, C, Heuer, A, Hezam, K, Hinneh, TK, Hiraike, Y, Hoan, NQ, Holla, R, Hon, J, Hoque, ME, Horita, N, Hossain, S, Hosseini, SE, Hosseinzadeh, H, Hosseinzadeh, M, Hostiuc, M, Hostiuc, S, Hoven, H, Hsairi, M, Hsu, JM, Hu, C, Huang, J, Huda, MN, Hulland, EN, Hultström, M, Hushmandi, K, Hussain, J, Hussein, NR, Huynh, CK, Huynh, H-H, Ibitoye, SE, Idowu, OO, Ihler, AL, Ikeda, N, Ikuta, KS, Ilesanmi, OS, Ilic, IM, Ilic, MD, Imam, MT, Immurana, M, Inbaraj, LR, Irham, LM, Isa, MA, Islam, MR, Ismail, F, Ismail, NE, Iso, H, Isola, G, Iwagami, M, Iwu, CCD, Iwu-Jaja, CJ, J, V, Jaafari, J, Jacob, L, Jacobsen, KH, Jadidi-Niaragh, F, Jahankhani, K, Jahanmehr, N, Jahrami, H, Jain, A, Jain, N, Jairoun, AA, Jaiswal, A, Jakovljevic, M, Jalilzadeh Yengejeh, R, Jamora, RDG, Jatau, AI, Javadov, S, Javaheri, T, Jayaram, S, Jeganathan, J, Jeswani, BM, Jiang, H, Johnson, CO, Jokar, M, Jomehzadeh, N, Jonas, JB, Joo, T, Joseph, A, Joseph, N, Joshi, V, Joshua, CE, Jozwiak, JJ, Jürisson, M, Kaambwa, B, Kabir, A, Kabir, Z, Kadashetti, V, Kahn, EM, Kalani, R, Kaliyadan, F, Kalra, S, Kamath, R, Kanagasabai, T, Kanchan, T, Kandel, H, Kanmiki, EW, Kanmodi, KK, Kansal, SK, Kapner, DJ, Kapoor, N, Karagiannidis, E, Karajizadeh, M, Karakasis, P, Karanth, SD, Karaye, IM, Karch, A, Karim, A, Karimi, H, Karmakar, S, Kashoo, FZ, Kasraei, H, Kassahun, WD, Kassebaum, NJ, Kassel, MB, Katikireddi, SV, Kauppila, JH, Kawakami, N, Kaydi, N, Kayode, GA, Kazemi, F, Keiyoro, PN, Kemmer, L, Kempen, JH, Kerr, JA, Kesse-Guyot, E, Khader, YS, Khafaie, MA, Khajuria, H, Khalaji, A, Khalil, M, Khalilian, A, Khamesipour, F, Khan, A, Khan, MN, Khan, M, Khan, MJ, Khan, MAB, Khanmohammadi, S, Khatab, K, Khatatbeh, H, Khatatbeh, MM, Khatib, MN, Khavandegar, A, Khayat Kashani, HR, Khidri, FF, Khodadoust, E, Khormali, M, Khorrami, Z, Khosla, AA, Khosrowjerdi, M, Khreis, H, Khusun, H, Kifle, ZD, Kim, K, Kim, MS, Kim, YJ, Kimokoti, RW, Kisa, A, Kisa, S, Knibbs, LD, Knudsen, AKS, Koh, DSQ, Kolahi, A-A, Kompani, F, Kong, J, Koren, G, Korja, M, Korshunov, VA, Korzh, O, Kosen, S, Kothari, N, Koul, PA, Koulmane Laxminarayana, SL, Krishan, K, Krishnamoorthy, V, Krishnamoorthy, Y, Krishnan, B, Krohn, KJ, Kuate Defo, B, Kucuk Bicer, B, Kuddus, MA, Kuddus, M, Kugbey, N, Kuitunen, I, Kulimbet, M, Kulkarni, V, Kumar, A, Kumar, N, Kumar, V, Kundu, S, Kurmi, OP, Kusnali, A, Kusuma, D, Kutluk, T, La Vecchia, C, Ladan, MA, Laflamme, L, Lahariya, C, Lai, DTC, Lal, DK, Lallukka, T, Lám, J, Lan, Q, Lan, T, Landires, I, Lanfranchi, F, Langguth, B, Lansingh, VC, Laplante-Lévesque, A, Larijani, B, Larsson, AO, Lasrado, S, Lauriola, P, Le, H-H, Le, LKD, Le, NHH, Le, TTT, Leasher, JL, Ledda, C, Lee, M, Lee, PH, Lee, SW, Lee, SWH, Lee, YH, LeGrand, KE, Leigh, J, Leong, E, Lerango, TL, Lescinsky, H, Leung, J, Li, M-C, Li, W-Z, Li, W, Li, Y, Li, Z, Ligade, VS, Lim, L-L, Lim, SS, Lin, R-T, Lin, S, Liu, C, Liu, G, Liu, J, Liu, RT, Liu, S, Liu, W, Liu, X, Livingstone, KM, Llanaj, E, Lohiya, A, López-Bueno, R, Lopukhov, PD, Lorkowski, S, Lotufo, PA, Lozano, R, Lubinda, J, Lucchetti, G, Luo, L, lv, H, M Amin, HI, Ma, ZF, Maass, KL, Mabrok, M, Machairas, N, Machoy, M, Mafhoumi, A, Magdy Abd El Razek, M, Maghazachi, AA, Mahadeshwara Prasad, DR, Maharaj, SB, Mahmoud, MA, Mahmoudi, E, Majeed, A, Makram, OM, Makris, KC, Malasala, S, Maled, V, Malhotra, K, Malik, AA, Malik, I, Malinga, LA, Malta, DC, Mamun, AA, Manda, AL, Manla, Y, Mansour, A, Mansouri, B, Mansouri, P, Mansourian, M, Mansournia, MA, Mantovani, LG, Manu, E, Marateb, HR, Maravilla, JC, Marsh, E, Martinez, G, Martinez-Piedra, R, Martini, S, Martins-Melo, FR, Martorell, M, Marx, W, Maryam, S, Mathangasinghe, Y, Mathioudakis, AG, Matozinhos, FP, Mattumpuram, J, Maugeri, A, Maulik, PK, Mayeli, M, Mazidi, M, Mazzotti, A, McGrath, JJ, McKee, M, McKowen, ALW, McLaughlin, SA, McPhail, MA, McPhail, SM, Mechili, EA, Mehmood, A, Mehmood, K, Mehrabani-Zeinabad, K, Mehrabi Nasab, E, Meier, T, Mejia-Rodriguez, F, Mekene Meto, T, Mekonnen, BD, Menezes, RG, Mengist, B, Mensah, GA, Mensah, LG, Mentis, A-FA, Meo, SA, Meretoja, A, Meretoja, TJ, Mersha, AM, Mesfin, BA, Mestrovic, T, Mettananda, KCD, Mettananda, S, Miazgowski, T, Micha, G, Michalek, IM, Micheletti Gomide Nogueira de Sá, AC, Miller, TR, Mirarefin, M, Mirghafourvand, M, Mirica, A, Mirijello, A, Mirrakhimov, EM, Mirshahi, A, Mirzaei, M, Mishra, AK, Mishra, V, Mitchell, PB, Mithra, P, Mittal, C, Moazen, B, Moberg, ME, Mocciaro, G, Mohamadkhani, A, Mohamed, AZ, Mohamed, AI, Mohamed, J, Mohamed, MFH, Mohamed, NS, Mohammadi, E, Mohammadi, S, Mohammadian-Hafshejani, A, Mohammadifard, N, Mohammed, H, Mohammed, M, Mohammed, S, Mokdad, AH, Monasta, L, Mondello, S, Moni, MA, Moodi Ghalibaf, A, Moore, CE, Moradi, M, Moradi, Y, Moraga, P, Morawska, L, Moreira, RS, Morovatdar, N, Morrison, SD, Morze, J, Mosaddeghi Heris, R, Mossialos, E, Motappa, R, Mougin, V, Mousavi, P, Msherghi, A, Mubarik, S, Muccioli, L, Mueller, UO, Mulita, F, Mullany, EC, Munjal, K, Murillo-Zamora, E, Murlimanju, BV, Musina, A-M, Mustafa, G, Muthu, S, Muthupandian, S, Muthusamy, R, Muzaffar, M, Myung, W, Nafei, A, Nagarajan, AJ, Nagaraju, SP, Nagel, G, Naghavi, M, Naghavi, P, Naik, GR, Naik, G, Nainu, F, Nair, TS, Najdaghi, S, Nakhostin Ansari, N, Nanavaty, DP, Nangia, V, Narasimha Swamy, S, Narimani Davani, D, Nascimento, BR, Nascimento, GG, Nashwan, AJ, Natto, ZS, Nauman, J, Navaratna, SNK, Naveed, M, Nayak, BP, Nayak, VC, Ndejjo, R, Nduaguba, SO, Negash, H, Negoi, I, Negoi, RI, Nejadghaderi, SA, Nejjari, C, Nematollahi, MH, Nepal, S, Neupane, S, Ng, M, Nguefack-Tsague, G, Ngunjiri, JW, Nguyen, DH, Nguyen, NNY, Nguyen, PT, Nguyen, VT, Nguyen Tran Minh, D, Niazi, RK, Nicholson, SI, Nie, J, Nikoobar, A, Nikpoor, AR, Ningrum, DNA, Nnaji, CA, Noman, EA, Nomura, S, Noroozi, N, Norrving, B, Noubiap, JJ, Nri-Ezedi, CA, Ntaios, G, Ntsekhe, M, Nunemo, MH, Nurrika, D, Nutor, JJ, Oancea, B, O'Connell, EM, Odetokun, IA, O'Donnell, MJ, Oduro, MS, Ogunfowokan, AA, Ogunkoya, A, Oh, I-H, Okati-Aliabad, H, Okeke, SR, Okekunle, AP, Okonji, OC, Olagunju, AT, Olasupo, OO, Olatubi, MI, Oliveira, AB, Oliveira, GMM, Olorukooba, AA, Olufadewa, II, Olusanya, BO, Olusanya, JO, Oluwafemi, YD, Omar, HA, Omar Bali, A, Omer, GL, Ong, KL, Ong, S, Onwujekwe, OE, Onyedibe, KI, Oppong, AF, Ordak, M, Orish, VN, Ornello, R, Orpana, HM, Ortiz, A, Ortiz-Prado, E, Osman, WMS, Ostroff, SM, Osuagwu, UL, Otoiu, A, Otstavnov, N, Otstavnov, SS, Ouyahia, A, Owolabi, MO, Oyeyemi, IT, Oyeyemi, OT, P A, MP, Pacheco-Barrios, K, Padron-Monedero, A, Padubidri, JR, Pal, PK, Palicz, T, Pan, F, Pan, H-F, Pana, A, Panda, SK, Panda-Jonas, S, Pandey, A, Pandi-Perumal, SR, Pangaribuan, HU, Pantazopoulos, I, Pantea Stoian, AM, Papadopoulou, P, Parent, MC, Parija, PP, Parikh, RR, Park, S, Parsons, N, Pashaei, A, Pasovic, M, Passera, R, Patil, S, Patoulias, D, Patthipati, VS, Paudel, U, Pawar, S, Pazoki Toroudi, H, Peden, AE, Pedersini, P, Peng, M, Pensato, U, Pepito, VCF, Peprah, EK, Peprah, P, Peres, MFP, Perianayagam, A, Perico, N, Perna, S, Pesudovs, K, Petcu, I-R, Petermann-Rocha, FE, Pham, HT, Philip, AK, Phillips, MR, Pickering, BV, Pierannunzio, D, Pigeolet, M, Pigott, DM, Piracha, ZZ, Piradov, MA, 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YF, Wiangkham, T, Wickramasinghe, ND, Wilkerson, C, Willeit, P, Wilson, S, Wong, YJ, Wongsin, U, Wozniak, S, Wu, C, Wu, D, Wu, F, Wu, Z, Xia, J, Xiao, H, Xu, S, Xu, X, Xu, YY, Yadav, MK, Yaghoubi, S, Yamagishi, K, Yang, L, Yano, Y, Yaribeygi, H, Yasufuku, Y, Ye, P, Yesodharan, R, Yesuf, SA, Yezli, S, Yi, S, Yiğit, A, Yigzaw, ZA, Yin, D, Yip, P, Yismaw, MB, Yon, DK, Yonemoto, N, You, Y, Younis, MZ, Yousefi, Z, Yu, C, Yu, Y, Zadey, S, Zadnik, V, Zakham, F, Zaki, N, Zakzuk, J, Zamagni, G, Zaman, SB, Zandieh, GGZ, Zanghì, A, Zar, HJ, Zare, I, Zarimeidani, F, Zastrozhin, MS, Zeng, Y, Zhai, C, Zhang, AL, Zhang, H, Zhang, L, Zhang, M, Zhang, Y, Zhang, Z, Zhang, Z-J, Zhao, H, Zhao, JT, Zhao, X-JG, Zhao, Y, Zhong, C, Zhou, J, Zhou, S, Zhu, B, Zhu, L, Zhu, Z, Ziaeian, B, Ziafati, M, Zielińska, M, Zimsen, SRM, Zoghi, G, Zoller, T, Zumla, A, Zyoud, SH, Murray, CJL, and Gakidou, E
Published: 2024

2. Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

Author: Vollset, SE, Ababneh, HS, Abate, YH, Abbafati, C, Abbasgholizadeh, R, Abbasian, M, Abbastabar, H, Abd Al Magied, AHA, Abd ElHafeez, S, Abdelkader, A, Abdelmasseh, M, Abd-Elsalam, S, Abdi, P, Abdollahi, M, Abdoun, M, Abdullahi, A, Abebe, M, Abiodun, O, Aboagye, RG, Abolhassani, H, Abouzid, M, Aboye, GB, Abreu, LG, Absalan, A, Abualruz, H, Abubakar, B, Abukhadijah, HJJ, Addolorato, G, Adekanmbi, V, Adetunji, CO, Adetunji, JB, Adeyeoluwa, TE, Adha, R, Adhikary, RK, Adnani, QES, Adzigbli, LA, Afrashteh, F, Afzal, MS, Afzal, S, Agbozo, F, Agodi, A, Agrawal, A, Agyemang-Duah, W, Ahinkorah, BO, Ahlstrom, AJ, Ahmad, A, Ahmad, F, Ahmad, MM, Ahmad, S, Ahmed, A, Ahmed, H, Ahmed, S, Ahmed, SA, Akinosoglou, K, Akkaif, MA, Akrami, AE, Akter, E, Al Awaidy, S, Al Hasan, SM, Al Mosa, AS, Al Ta'ani, O, Al Zaabi, OAM, Alahdab, F, Alajlani, MM, Al-Ajlouni, Y, Alalalmeh, SO, Al-Aly, Z, Alam, K, Alam, N, Alam, T, Alam, Z, Al-amer, RM, Alanezi, FM, Alanzi, TM, Albakri, A, Aldhaleei, WA, Aldridge, RW, Alemohammad, SY, Alemu, YM, Al-Gheethi, AAS, Al-Hanawi, MK, Ali, A, Ali, I, Ali, MU, Ali, R, Ali, SSS, Ali, VE, Ali, W, Al-Ibraheem, A, Alicandro, G, Alif, SM, Aljunid, SM, Alla, F, Almazan, JU, Al-Mekhlafi, HM, Alqutaibi, AY, Alrawashdeh, A, Alrousan, SM, Al-Sabah, SK, Alsabri, MA, Altaany, Z, Al-Tammemi, AB, Al-Tawfiq, JA, Altirkawi, KA, Aluh, DO, Alvis-Guzman, N, Al-Wardat, MS, Al-Worafi, YM, Aly, H, Alyahya, MS, Alzoubi, KH, Al-Zyoud, W, Amani, R, Ameyaw, EK, Amin, TT, Amindarolzarbi, A, Amiri, S, Amirzade-Iranaq, MH, Amu, H, Amugsi, DA, Ancuceanu, R, Anderlini, D, Anderson, DB, Andrade, PP, Andrei, CL, Andrei, T, Andrews, EA, Anil, A, Anil, S, Anoushiravani, A, Antony, CM, Antriyandarti, E, Anuoluwa, BS, Anvari, S, Anyasodor, AE, Appiah, F, Aquilano, M, Arab, JP, Arabloo, J, Arafa, EA, Arafat, M, Aravkin, AY, Ardekani, A, Areda, D, Aregawi, BB, Aremu, A, Ariffin, H, Arkew, M, Armani, K, Artamonov, AA, Arumugam, A, Asghari-Jafarabadi, M, Ashbaugh, C, Astell-Burt, T, Athari, SS, 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Rao, M, Rasella, D, Rashedi, V, Rashid, AM, Rasouli-Saravani, A, Rastogi, P, Rasul, A, Rathish, D, Rathnaiah Babu, G, Rauniyar, SK, Ravangard, R, Rawaf, DL, Rawaf, S, Raza, RZ, Redwan, EMM, Reifels, L, Reitsma, MB, Remuzzi, G, Rengasamy, KRR, Reshmi, B, Resnikoff, S, Restaino, S, Reyes, LF, Rezaei, N, Rezaei, ZS, Rezaeian, M, Rhee, TG, Rickard, J, Robalik, T, Robinson-Oden, HE, Rocha, HAL, Rodrigues, M, Rodriguez, JAB, Roever, L, Romadlon, DS, Ronfani, L, Rony, MKK, Roshandel, G, Rotimi, K, Rout, HS, Roy, B, Rubagotti, E, Ruela, GDA, Rumisha, SF, Runghien, T, Russo, M, Saad, AMA, Saber, K, Saber-Ayad, MM, Sabet, CJ, Sabour, S, Sachdev, PS, Saddler, A, Sadee, BA, Sadeghi, M, Saeb, MR, Saeed, U, Safi, SZ, Sagar, R, Saghafi, A, Sagoe, D, Sahebkar, A, Sahoo, PM, Sajid, MR, Salam, N, Salamati, P, Salami, AA, Saleh, MA, Salehi, L, Salem, MR, Salemcity, AJ, Salimi, S, Samadi Kafil, H, Samargandy, S, Samodra, YL, Samy, AM, Sanabria, J, Sanna, F, Santric-Milicevic, MM, Sao Jose, BP, Saraswathy, SYI, Saravanan, A, Sarmiento-Suárez, R, Sarode, GS, Sarode, SC, Sartorius, B, Satpathy, M, Sayeed, A, Scarmeas, N, Schaarschmidt, BM, Schinckus, C, Schuermans, A, Schumacher, AE, Schutte, AE, Schwebel, DC, Schwendicke, F, Selvaraj, S, Semreen, MH, Senapati, S, Sengupta, P, Senthilkumaran, S, Serban, D, Sethi, Y, Seylani, A, Shafie, M, Shah, PA, Shahbandi, A, Shahid, S, Shahid, W, Shahsavari, HR, Shahwan, MJ, Shaikh, MA, Shalash, AS, Shamekh, A, Shamim, MA, Shanawaz, M, Shankar, A, Shannawaz, M, Sharath, M, Sharfaei, S, Sharifan, A, Sharifi-Rad, J, Sharma, A, Sharma, M, Sharma, S, Sharma, V, Shastry, RP, Shayan, M, Shekhar, S, Shenoy, RR, Shetty, M, Shetty, PH, Shetty, PK, Shi, P, Shiani, A, Shigematsu, M, Shimels, T, Shiri, R, Shittu, A, Shiue, I, Shivakumar, KM, Shool, S, Shorofi, SA, Shrestha, S, Shuval, K, Si, Y, Siddig, EE, Sidhu, JK, Silva, JP, Silva, LMLR, Silva, S, Silva, TPR, Simpson, CR, Simpson, KE, Singh, A, Singh, BB, Singh, B, Singh, H, Singh, J, Singh, P, Skou, ST, Smith, G, Sobia, F, Socea, B, Solanki, S, Soleimani, H, Soliman, SSM, Song, Y, Soyiri, IN, Spartalis, M, Spearman, S, Sreeramareddy, CT, Stanaway, JD, Stanikzai, MH, Starodubova, AV, Stein, DJ, Steiner, C, Steiropoulos, P, Stockfelt, L, Stokes, MA, Straif, K, Subedi, N, Suliankatchi Abdulkader, R, Sultana, A, Sun, J, Sundström, J, Swain, CK, Szarpak, L, Szeto, MD, Tabaee Damavandi, P, Tabarés-Seisdedos, R, Tabatabaei Malazy, O, Tabatabaeizadeh, S-A, Tabatabai, S, Tabb, KM, Tabche, C, Tabish, M, Taheri Abkenar, Y, Taheri Soodejani, M, Taiba, J, Talaat, IM, Tamuzi, JL, Tan, K-K, Tang, H, Tat, NY, Tavakoli Oliaee, R, Tavangar, SM, Taveira, N, Tbakhi, A, Tehrani, H, Temsah, M-H, Teramoto, M, Tesfaye, BT, Teye-Kwadjo, E, Thangaraju, P, Thankappan, KR, Thapar, R, Thayakaran, R, Thirunavukkarasu, S, Thomas, N, Thygesen, LC, Ticoalu, JHV, Timalsena, D, Tiruye, TY, Tiwari, K, Tomo, S, Tonelli, M, Topor-Madry, R, Touvier, M, Tovani-Palone, MR, Tran, AT, Tran, JT, Tran, NM, Tran, TH, Trico, D, Tromans, SJ, Truyen, TTTT, Tsatsakis, A, Tsermpini, EE, Tumurkhuu, M, Turnock, ST, Udoh, A, Ullah, A, Ullah, S, Umakanthan, S, Umar, M, Umar, SS, Unim, B, Unnikrishnan, B, Upadhyay, E, Usman, JS, Vahdati, S, Vaithinathan, AG, Vakili, O, Valizadeh, R, Van den Eynde, J, Vart, P, Varthya, SB, Vasankari, TJ, Vasic, M, Venketasubramanian, N, Veroux, M, Verras, G-I, Vervoort, D, Vijayageetha, M, Villafañe, JH, Vinayak, M, Violante, FS, Vladimirov, SK, Vlassov, V, Vo, B, Vohra, K, Vos, T, Wadood, AW, Waheed, Y, Wang, F, Wang, S, Wang, Y, Wang, Y-P, Wanjau, MN, Waqas, M, Ward, P, Waris, A, Wassie, EG, Watson, S, Weaver, MR, Weerakoon, KG, Weintraub, RG, Weldetinsaa, HLL, Wells, KM, Wen, YF, Westerman, R, Wiangkham, T, Wickramasinghe, DP, Widowati, E, Wojewodzic, MW, Woldeyes, DH, Wolf, AW, Wolfe, CDA, Wu, C, Wu, D, Wu, F, Wu, J, Wu, Z, Wulf Hanson, S, Xiao, H, Xu, S, Yadav, R, Yamagishi, K, Yang, D, Yano, Y, Yarahmadi, A, Yazdani Nia, I, Ye, P, Yesodharan, R, Yesuf, SA, Yezli, S, Yiğit, A, Yiğit, V, Yigzaw, ZA, Yin, D, Yip, P, Yonemoto, N, You, Y, Younis, MZ, Yu, C, Yu, EA, Yu, Y, Yuan, C-W, Yusuf, H, Zafar, U, Zafari, N, Zahid, MH, Zakham, F, Zaki, N, Zerfu, TA, Zhang, H, Zhang, J, Zhang, L, Zhang, Y, Zhang, Z, Zhao, X-JG, Zhao, Y, Zhao, Z, Zhong, C, Zhou, B, Zhou, J, Zhou, S, Zhu, B, Zhumagaliuly, A, Zielińska, M, Zoghi, G, Zumla, A, Zyoud, SH, Smith, AE, and Murray, CJL
Published: 2024

3. AusTrakka: Fast-tracking nationalized genomics surveillance in response to the COVID-19 pandemic

Author: Hoang, T, da Silva, AG, Jennison, A, Williamson, DA, Howden, BP, Seemann, T, Hoang, T, da Silva, AG, Jennison, A, Williamson, DA, Howden, BP, and Seemann, T
Abstract: The COVID-19 pandemic has driven demand for integrated genomics, resulting in fast-tracked development of AusTrakka, Australia’s pathogen genomics platform. This facilitated rapid data sharing, democratised access to computational and bioinformatic resources and expertise, and achieved national real-time genomic surveillance.
Published: 2022

4. Future-proofing and maximizing the utility of metadata: The PHA4GE SARS-CoV-2 contextual data specification package.

Author: Griffiths, EJ, Timme, RE, Mendes, CI, Page, AJ, Alikhan, N-F, Fornika, D, Maguire, F, Campos, J, Park, D, Olawoye, IB, Oluniyi, PE, Anderson, D, Christoffels, A, da Silva, AG, Cameron, R, Dooley, D, Katz, LS, Black, A, Karsch-Mizrachi, I, Barrett, T, Johnston, A, Connor, TR, Nicholls, SM, Witney, AA, Tyson, GH, Tausch, SH, Raphenya, AR, Alcock, B, Aanensen, DM, Hodcroft, E, Hsiao, WWL, Vasconcelos, ATR, MacCannell, DR, Griffiths, EJ, Timme, RE, Mendes, CI, Page, AJ, Alikhan, N-F, Fornika, D, Maguire, F, Campos, J, Park, D, Olawoye, IB, Oluniyi, PE, Anderson, D, Christoffels, A, da Silva, AG, Cameron, R, Dooley, D, Katz, LS, Black, A, Karsch-Mizrachi, I, Barrett, T, Johnston, A, Connor, TR, Nicholls, SM, Witney, AA, Tyson, GH, Tausch, SH, Raphenya, AR, Alcock, B, Aanensen, DM, Hodcroft, E, Hsiao, WWL, Vasconcelos, ATR, and MacCannell, DR
Abstract: BACKGROUND: The Public Health Alliance for Genomic Epidemiology (PHA4GE) (https://pha4ge.org) is a global coalition that is actively working to establish consensus standards, document and share best practices, improve the availability of critical bioinformatics tools and resources, and advocate for greater openness, interoperability, accessibility, and reproducibility in public health microbial bioinformatics. In the face of the current pandemic, PHA4GE has identified a need for a fit-for-purpose, open-source SARS-CoV-2 contextual data standard. RESULTS: As such, we have developed a SARS-CoV-2 contextual data specification package based on harmonizable, publicly available community standards. The specification can be implemented via a collection template, as well as an array of protocols and tools to support both the harmonization and submission of sequence data and contextual information to public biorepositories. CONCLUSIONS: Well-structured, rich contextual data add value, promote reuse, and enable aggregation and integration of disparate datasets. Adoption of the proposed standard and practices will better enable interoperability between datasets and systems, improve the consistency and utility of generated data, and ultimately facilitate novel insights and discoveries in SARS-CoV-2 and COVID-19. The package is now supported by the NCBI's BioSample database.
Published: 2022

5. What do we know about violence against women in pandemic times? Insights based on search trends

Author: Loureiro Ff, Silva Teles Al, Guatimosim Rf, Leandro Fernandes Malloy-Diniz, da Silva Ag, and de Miranda Dm
Subjects: History, Coronavirus disease 2019 (COVID-19), Pandemic, Complaint, medicine, Domestic violence, Criminology, Social isolation, medicine.symptom
Abstract: PurposeThis short communication aims to assess the situation of domestic violence against women in Brazil during social isolation due to the COVID-19 pandemic.MethodsWe extracted data from Google Trends showing the magnitude of searches on the topics domestic violence and complaint and then compared with the data of the complaint reports.ResultsSearches on Google containing those terms have increased while the complaints reports against domestic violence have decreased.ConclusionThe growth of searches about domestic violence and domestic violence complaints indicates the possibility of a real rise in this type of violence in Brazil.
Published: 2021

6. Genomic Epidemiology and Antimicrobial Resistance Mechanisms of Imported Typhoid in Australia

Author: Ingle, DJ, Andersson, P, Valcanis, M, Wilmot, M, Easton, M, Lane, C, Barden, J, da Silva, AG, Seemann, T, Horan, K, Ballard, SA, Sherry, NL, Williamson, DA, Howden, BP, Ingle, DJ, Andersson, P, Valcanis, M, Wilmot, M, Easton, M, Lane, C, Barden, J, da Silva, AG, Seemann, T, Horan, K, Ballard, SA, Sherry, NL, Williamson, DA, and Howden, BP
Abstract: Typhoid fever is an invasive bacterial disease of humans that disproportionately affects low- and middle-income countries. Antimicrobial resistance (AMR) has been increasingly prevalent in recent decades in Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever, limiting treatment options. In Australia, most cases of typhoid fever are imported due to travel to regions where typhoid fever is endemic. Here, all 116 isolates of S. Typhi isolated in Victoria, Australia, between 1 July 2018 and 30 June 2020, underwent whole-genome sequencing and antimicrobial susceptibility testing. Genomic data were linked to international travel data collected from routine case interviews. Travel to South Asia accounted for most cases, with 92.2% imported from seven primary countries (the top two were India, n = 87, and Pakistan, n = 12). A total of 17 S. Typhi genotypes were detected in the 2-year cohort, with 48.2% genotyped as part of global AMR lineages. Ciprofloxacin resistance was detected in two lineages, 3.3 and 4.3.1.2, all from cases with reported travel to India. Nearly all multidrug and extensively drug resistant isolates (90%) were from cases with reported travel to Pakistan in genotypes 4.3.1.1 and 4.3.1.1.P1. Extended spectrum beta-lactamases, blaCTX-M-15 and blaSHV-12, were detected in cases with travel to Pakistan and India, respectively. Linking epidemiological data with genomic studies of S. Typhi provides an opportunity to improve understanding of the emergence, spread and risk of drug-resistant S. Typhi infections and to better inform empirical treatment guidelines in returned travelers.
Published: 2021

7. Genomics-informed responses in the elimination of COVID-19 in Victoria, Australia: an observational, genomic epidemiological study

Author: Lane, CR, Sherry, NL, Porter, AF, Duchene, S, Horan, K, Andersson, P, Wilmot, M, Turner, A, Dougall, S, Johnson, SA, Sait, M, da Silva, AG, Ballard, SA, Hoang, T, Stinear, TP, Caly, L, Sintchenko, V, Graham, R, McMahon, J, Smith, D, Leong, LEX, Meumann, EM, Cooley, L, Schwessinger, B, Rawlinson, W, van Hal, SJ, Stephens, N, Catton, M, Looker, C, Crouch, S, Sutton, B, Alpren, C, Williamson, DA, Seemann, T, Howden, BP, Lane, CR, Sherry, NL, Porter, AF, Duchene, S, Horan, K, Andersson, P, Wilmot, M, Turner, A, Dougall, S, Johnson, SA, Sait, M, da Silva, AG, Ballard, SA, Hoang, T, Stinear, TP, Caly, L, Sintchenko, V, Graham, R, McMahon, J, Smith, D, Leong, LEX, Meumann, EM, Cooley, L, Schwessinger, B, Rawlinson, W, van Hal, SJ, Stephens, N, Catton, M, Looker, C, Crouch, S, Sutton, B, Alpren, C, Williamson, DA, Seemann, T, and Howden, BP
Abstract: BACKGROUND: A cornerstone of Australia's ability to control COVID-19 has been effective border control with an extensive supervised quarantine programme. However, a rapid recrudescence of COVID-19 was observed in the state of Victoria in June, 2020. We aim to describe the genomic findings that located the source of this second wave and show the role of genomic epidemiology in the successful elimination of COVID-19 for a second time in Australia. METHODS: In this observational, genomic epidemiological study, we did genomic sequencing of all laboratory-confirmed cases of COVID-19 diagnosed in Victoria, Australia between Jan 25, 2020, and Jan 31, 2021. We did phylogenetic analyses, genomic cluster discovery, and integrated results with epidemiological data (detailed information on demographics, risk factors, and exposure) collected via interview by the Victorian Government Department of Health. Genomic transmission networks were used to group multiple genomic clusters when epidemiological and genomic data suggested they arose from a single importation event and diversified within Victoria. To identify transmission of emergent lineages between Victoria and other states or territories in Australia, all publicly available SARS-CoV-2 sequences uploaded before Feb 11, 2021, were obtained from the national sequence sharing programme AusTrakka, and epidemiological data were obtained from the submitting laboratories. We did phylodynamic analyses to estimate the growth rate, doubling time, and number of days from the first local infection to the collection of the first sequenced genome for the dominant local cluster, and compared our growth estimates to previously published estimates from a similar growth phase of lineage B.1.1.7 (also known as the Alpha variant) in the UK. FINDINGS: Between Jan 25, 2020, and Jan 31, 2021, there were 20 451 laboratory-confirmed cases of COVID-19 in Victoria, Australia, of which 15 431 were submitted for sequencing, and 11 711 met all quality co
Published: 2021

8. Search and Contain: Impact of an Integrated Genomic and Epidemiological Surveillance and Response Program for Control of Carbapenemase-producing Enterobacterales

Author: Lane, CR, Brett, J, Schultz, M, Gorrie, CL, Stevens, K, Cameron, DRM, St George, S, van Diemen, A, Easton, M, Stuart, RL, Sait, M, Peleg, AY, Stewardson, AJ, Cheng, AC, Spelman, DW, Waters, MJ, Ballard, SA, Sherry, NL, Williamson, DA, Romanes, F, Sutton, B, Kwong, JC, Seemann, T, da Silva, AG, Stephens, N, Howden, BP, Lane, CR, Brett, J, Schultz, M, Gorrie, CL, Stevens, K, Cameron, DRM, St George, S, van Diemen, A, Easton, M, Stuart, RL, Sait, M, Peleg, AY, Stewardson, AJ, Cheng, AC, Spelman, DW, Waters, MJ, Ballard, SA, Sherry, NL, Williamson, DA, Romanes, F, Sutton, B, Kwong, JC, Seemann, T, da Silva, AG, Stephens, N, and Howden, BP
Abstract: BACKGROUND: Multiresistant organisms (MROs) pose a critical threat to public health. Population-based programs for control of MROs such as carbapenemase-producing Enterobacterales (CPE) have emerged and evaluation is needed. We assessed the feasibility and impact of a statewide CPE surveillance and response program deployed across Victoria, Australia (population 6.5 million). METHODS: A prospective multimodal intervention including active screening, carrier isolation, centralized case investigation, and comparative pathogen genomics was implemented. We analyzed trends in CPE incidence and clinical presentation, risk factors, and local transmission over the program's first 3 years (2016-2018). RESULTS: CPE case ascertainment increased over the study period to 1.42 cases/100 000 population, linked to increased screening without a concomitant rise in active clinical infections (0.45-0.60 infections/100 000 population, P = .640). KPC-2 infection decreased from 0.29 infections/100 000 population prior to intervention to 0.03 infections/100 000 population in 2018 (P = .003). Comprehensive case investigation identified instances of overseas community acquisition. Median time between isolate referral and genomic and epidemiological assessment for local transmission was 11 days (IQR, 9-14). Prospective surveillance identified numerous small transmission networks (median, 2; range, 1-19 cases), predominantly IMP and KPC, with median pairwise distance of 8 (IQR, 4-13) single nucleotide polymorphisms; low diversity between clusters of the same sequence type suggested genomic cluster definitions alone are insufficient for targeted response. CONCLUSIONS: We demonstrate the value of centralized CPE control programs to increase case ascertainment, resolve risk factors, and identify local transmission through prospective genomic and epidemiological surveillance; methodologies are transferable to low-prevalence settings and MROs globally.
Published: 2021

9. Evolutionary dynamics of multidrug resistant Salmonella enterica serovar 4,[5],12:i:- in Australia

Author: Ingle, DJ, Ambrose, RL, Baines, SL, Duchene, S, da Silva, AG, Lee, DYJ, Jones, M, Valcanis, M, Taiaroa, G, Ballard, SA, Kirk, MD, Howden, BP, Pearson, JS, Williamson, DA, Ingle, DJ, Ambrose, RL, Baines, SL, Duchene, S, da Silva, AG, Lee, DYJ, Jones, M, Valcanis, M, Taiaroa, G, Ballard, SA, Kirk, MD, Howden, BP, Pearson, JS, and Williamson, DA
Abstract: Salmonella enterica serovar 4,[5],12:i:- (Salmonella 4,[5],12:i:-) is a monophasic variant of Salmonella Typhimurium that has emerged as a global cause of multidrug resistant salmonellosis. We used Bayesian phylodynamics, genomic epidemiology, and phenotypic characterization to describe the emergence and evolution of Salmonella 4,[5],12:i:- in Australia. We show that the interruption of the genetic region surrounding the phase II flagellin, FljB, causing a monophasic phenotype, represents a stepwise evolutionary event through the accumulation of mobile resistance elements with minimal impairment to bacterial fitness. We identify three lineages with different population dynamics and discrete antimicrobial resistance profiles emerged, likely reflecting differential antimicrobial selection pressures. Two lineages are associated with travel to South-East Asia and the third lineage is endemic to Australia. Moreover antimicrobial-resistant Salmonella 4,[5],12:i- lineages efficiently infected and survived in host phagocytes and epithelial cells without eliciting significant cellular cytotoxicity, suggesting a suppression of host immune response that may facilitate the persistence of Salmonella 4,[5],12:i:-.
Published: 2021

10. An implementation science approach to evaluating pathogen whole genome sequencing in public health

Author: Ferdinand, AS, Kelaher, M, Lane, CR, da Silva, AG, Sherry, NL, Ballard, SA, Andersson, P, Hoang, T, Denholm, JT, Easton, M, Howden, BP, Williamson, DA, Ferdinand, AS, Kelaher, M, Lane, CR, da Silva, AG, Sherry, NL, Ballard, SA, Andersson, P, Hoang, T, Denholm, JT, Easton, M, Howden, BP, and Williamson, DA
Abstract: BACKGROUND: Pathogen whole genome sequencing (WGS) is being incorporated into public health surveillance and disease control systems worldwide and has the potential to make significant contributions to infectious disease surveillance, outbreak investigation and infection prevention and control. However, to date, there are limited data regarding (i) the optimal models for integration of genomic data into epidemiological investigations and (ii) how to quantify and evaluate public health impacts resulting from genomic epidemiological investigations. METHODS: We developed the Pathogen Genomics in Public HeAlth Surveillance Evaluation (PG-PHASE) Framework to guide examination of the use of WGS in public health surveillance and disease control. We illustrate the use of this framework with three pathogens as case studies: Listeria monocytogenes, Mycobacterium tuberculosis and SARS-CoV-2. RESULTS: The framework utilises an adaptable whole-of-system approach towards understanding how interconnected elements in the public health application of pathogen genomics contribute to public health processes and outcomes. The three phases of the PG-PHASE Framework are designed to support understanding of WGS laboratory processes, analysis, reporting and data sharing, and how genomic data are utilised in public health practice across all stages, from the decision to send an isolate or sample for sequencing to the use of sequence data in public health surveillance, investigation and decision-making. Importantly, the phases can be used separately or in conjunction, depending on the need of the evaluator. Subsequent to conducting evaluation underpinned by the framework, avenues may be developed for strategic investment or interventions to improve utilisation of whole genome sequencing. CONCLUSIONS: Comprehensive evaluation is critical to support health departments, public health laboratories and other stakeholders to successfully incorporate microbial genomics into public health practice.
Published: 2021

11. Complete microbial genomes for public health in Australia and the Southwest Pacific

Author: Baines, SL, da Silva, AG, Carter, GP, Jennison, A, Rathnayake, I, Graham, RM, Sintchenko, V, Wang, Q, Rockett, RJ, Timms, VJ, Martinez, E, Ballard, S, Tomita, T, Isles, N, Horan, KA, Pitchers, W, Stinear, TP, Williamson, DA, Howden, BP, Seemann, T, Baines, SL, da Silva, AG, Carter, GP, Jennison, A, Rathnayake, I, Graham, RM, Sintchenko, V, Wang, Q, Rockett, RJ, Timms, VJ, Martinez, E, Ballard, S, Tomita, T, Isles, N, Horan, KA, Pitchers, W, Stinear, TP, Williamson, DA, Howden, BP, and Seemann, T
Abstract: Complete genomes of microbial pathogens are essential for the phylogenomic analyses that increasingly underpin core public health laboratory activities. Here, we announce a BioProject (PRJNA556438) dedicated to sharing complete genomes chosen to represent a range of pathogenic bacteria with regional importance to Australia and the Southwest Pacific; enriching the catalogue of globally available complete genomes for public health while providing valuable strains to regional public health microbiology laboratories. In this first step, we present 26 complete high-quality bacterial genomes. Additionally, we describe here a framework for reconstructing complete microbial genomes and highlight some of the challenges and considerations for accurate and reproducible genome reconstruction.
Published: 2020

12. Prolonged Outbreak of Multidrug-Resistant Shigella sonnei Harboring bla(CTX-M-27) in Victoria, Australia

Author: Ingle, DJ, Andersson, P, Valcanis, M, Barnden, J, da Silva, AG, Horan, KA, Seemann, T, Easton, M, Williamson, DA, Sherry, NL, Howden, BP, Ingle, DJ, Andersson, P, Valcanis, M, Barnden, J, da Silva, AG, Horan, KA, Seemann, T, Easton, M, Williamson, DA, Sherry, NL, and Howden, BP
Abstract: In Australia, cases of shigellosis usually occur in returned travelers from regions of shigellosis endemicity or in men who have sex with men. Resistance to multiple antibiotics has significantly increased in Shigella sonnei isolates and represents a significant public health concern. We investigate an outbreak of multidrug-resistant S. sonnei in Victoria, Australia. We undertook whole-genome sequencing of 54 extended-spectrum-beta-lactamase (ESBL)-producing S. sonnei isolates received at the Microbiological Diagnostic Unit Public Health Laboratory between January 2019 and March 2020. The population structure and antimicrobial resistance profiles were identified by genomic analyses, with 73 previously characterized Australian S. sonnei isolates providing context. Epidemiological data, including age and sex of the shigellosis cases, were also collected. There was a significant increase in cases of ESBL S. sonnei from July 2019. Most of the ESBL S. sonnei isolates (65%) fell within a single cluster that was predominantly comprised of male cases that were characterized by the presence of the blaCTX-M-27 gene conferring resistance to extended-spectrum cephalosporins. These isolates were also multidrug resistant, including resistance to azithromycin and co-trimoxazole and reduced susceptibility to ciprofloxacin. Our data uncovered a prolonged clonal outbreak of ESBL S. sonnei infection that was likely first introduced by returned travelers and has subsequently been circulating locally in Australia. The emergence of a local outbreak of ESBL S. sonnei with a multidrug-resistant profile, including reduced susceptibility to ciprofloxacin, represents a significant public health threat.
Published: 2020

13. Systematic analysis of key parameters for genomics-based real-time detection and tracking of multidrug-resistant bacteria

Author: Gorrie, C, Da Silva, AG, Ingle, D, Higgs, C, Seemann, T, Stinear, T, Williamson, D, Kwong, J, Grayson, L, Sherry, N, Howden, B, Gorrie, C, Da Silva, AG, Ingle, D, Higgs, C, Seemann, T, Stinear, T, Williamson, D, Kwong, J, Grayson, L, Sherry, N, and Howden, B
Abstract: Background: Pairwise single nucleotide polymorphisms (SNPs) are a cornerstone for genomic approaches to multidrug-resistant organisms (MDROs) transmission inference in hospitals. However, the impact of key analysis parameters on these inferences has not been systematically analysed. Methods: We conducted a multi-hospital 15-month prospective study, sequencing 1537 MDRO genomes for comparison; methicillin-resistant Staphylococcus aureus , vancomycin-resistant Enterococcus faecium , and extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae . We systematically assessed the impact of sample and reference genome diversity, masking of prophage and regions of recombination, cumulative genome analysis compared to a three-month sliding-window, and the comparative effects each of these had when applying a SNP threshold for inferring likely transmission (≤15 SNPs for S. aureus , ≤25 for other species). Findings: Across the species, using a reference genome of the same sequence type provided a greater degree of pairwise SNP resolution, compared to species and outgroup-reference alignments that typically resulted in inflated SNP distances and the possibility of missed transmission events. Omitting prophage regions had minimal impacts, however, omitting recombination regions a highly variable effect, often inflating the number of closely related pairs. Estimating pairwise SNP distances was more consistent using a sliding-window than a cumulative approach. Interpretation: The use of a closely-related reference genome, without masking of prophage or recombination regions, and a sliding-window for isolate inclusion is best for accurate and consistent MDRO transmission inference. The increased stability and resolution provided by these approaches means SNP thresholds for putative transmission inference can be more reliably applied among diverse MDROs. Funding: This work was supported by the Melbourne Genomics Health Alliance (funded by the State Govern
Published: 2020

14. Tracking the COVID-19 pandemic in Australia using genomics

Author: Seemann, T, Lane, CR, Sherry, NL, Duchene, S, da Silva, AG, Caly, L, Sait, M, Ballard, SA, Horan, K, Schultz, MB, Hoang, T, Easton, M, Dougall, S, Stinear, TP, Druce, J, Catton, M, Sutton, B, van Diemen, A, Alpren, C, Williamson, DA, Howden, BP, Seemann, T, Lane, CR, Sherry, NL, Duchene, S, da Silva, AG, Caly, L, Sait, M, Ballard, SA, Horan, K, Schultz, MB, Hoang, T, Easton, M, Dougall, S, Stinear, TP, Druce, J, Catton, M, Sutton, B, van Diemen, A, Alpren, C, Williamson, DA, and Howden, BP
Abstract: Genomic sequencing has significant potential to inform public health management for SARS-CoV-2. Here we report high-throughput genomics for SARS-CoV-2, sequencing 80% of cases in Victoria, Australia (population 6.24 million) between 6 January and 14 April 2020 (total 1,333 COVID-19 cases). We integrate epidemiological, genomic and phylodynamic data to identify clusters and impact of interventions. The global diversity of SARS-CoV-2 is represented, consistent with multiple importations. Seventy-six distinct genomic clusters were identified, including large clusters associated with social venues, healthcare and cruise ships. Sequencing sequential samples from 98 patients reveals minimal intra-patient SARS-CoV-2 genomic diversity. Phylodynamic modelling indicates a significant reduction in the effective viral reproductive number (Re) from 1.63 to 0.48 after implementing travel restrictions and physical distancing. Our data provide a concrete framework for the use of SARS-CoV-2 genomics in public health responses, including its use to rapidly identify SARS-CoV-2 transmission chains, increasingly important as social restrictions ease globally.
Published: 2020

15. Remodeling of pSK1 Family Plasmids and Enhanced Chlorhexidine Tolerance in a Dominant Hospital Lineage of Methicillin-Resistant Staphylococcus aureus

Author: Baines, SL, Jensen, SO, Firth, N, da Silva, AG, Seemann, T, Carter, GP, Williamson, DA, Howden, BP, Stinear, TP, Baines, SL, Jensen, SO, Firth, N, da Silva, AG, Seemann, T, Carter, GP, Williamson, DA, Howden, BP, and Stinear, TP
Abstract: Staphylococcus aureus is a significant human pathogen whose evolution and adaptation have been shaped in part by mobile genetic elements (MGEs), facilitating the global spread of extensive antimicrobial resistance. However, our understanding of the evolutionary dynamics surrounding MGEs, in particular, how changes in the structure of multidrug resistance (MDR) plasmids may influence important staphylococcal phenotypes, is incomplete. Here, we undertook a population and functional genomics study of 212 methicillin-resistant S. aureus (MRSA) sequence type 239 (ST239) isolates collected over 32 years to explore the evolution of the pSK1 family of MDR plasmids, illustrating how these plasmids have coevolved with and contributed to the successful adaptation of this persistent MRSA lineage. Using complete genomes and temporal phylogenomics, we reconstructed the evolution of the pSK1 family lineage from its emergence in the late 1970s and found that multiple structural variants have arisen. Plasmid maintenance and stability were linked to IS256- and IS257-mediated chromosomal integration and disruption of the plasmid replication machinery. Overlaying genomic comparisons with phenotypic susceptibility data for gentamicin, trimethoprim, and chlorhexidine, it appeared that pSK1 has contributed to enhanced resistance in ST239 MRSA isolates through two mechanisms: (i) acquisition of plasmid-borne resistance mechanisms increasing the rates of gentamicin resistance and reduced chlorhexidine susceptibility and (ii) changes in the plasmid configuration linked with further enhancement of chlorhexidine tolerance. While the exact mechanism of enhanced tolerance remains elusive, this research has uncovered a potential evolutionary response of ST239 MRSA to biocides, one of which may contribute to the ongoing persistence and adaptation of this lineage within health care institutions.
Published: 2019

16. Mining the Methylome Reveals Extensive Diversity in Staphylococcus epidermidis Restriction Modification

Author: Torres, VJ, Lee, JYH, Carter, GP, Pidot, SJ, Guerillot, R, Seemann, T, da Silva, AG, Foster, TJ, Howden, BP, Stinear, TP, Monk, IR, Torres, VJ, Lee, JYH, Carter, GP, Pidot, SJ, Guerillot, R, Seemann, T, da Silva, AG, Foster, TJ, Howden, BP, Stinear, TP, and Monk, IR
Abstract: Staphylococcus epidermidis is a significant opportunistic pathogen of humans. Molecular studies in this species have been hampered by the presence of restriction-modification (RM) systems that limit introduction of foreign DNA. Here, we establish the complete genomes and methylomes for seven clinically significant, genetically diverse S. epidermidis isolates and perform the first systematic genomic analyses of the type I RM systems within both S. epidermidis and Staphylococcus aureus Our analyses revealed marked differences in the gene arrangement, chromosomal location, and movement of type I RM systems between the two species. Unlike S. aureus, S. epidermidis type I RM systems demonstrate extensive diversity even within a single genetic lineage. This is contrary to current assumptions and has important implications for approaching the genetic manipulation of S. epidermidis Using Escherichia coli plasmid artificial modification (PAM) to express S. epidermidishsdMS, we readily overcame restriction barriers in S. epidermidis and achieved electroporation efficiencies equivalent to those of modification-deficient mutants. With these functional experiments, we demonstrated how genomic data can be used to predict both the functionality of type I RM systems and the potential for a strain to be electroporation proficient. We outline an efficient approach for the genetic manipulation of S. epidermidis strains from diverse genetic backgrounds, including those that have hitherto been intractable. Additionally, we identified S. epidermidis BPH0736, a naturally restriction-defective, clinically significant, multidrug-resistant ST2 isolate, as an ideal candidate for molecular studies.IMPORTANCEStaphylococcus epidermidis is a major cause of hospital-acquired infections, especially those related to implanted medical devices. Understanding how S. epidermidis causes disease and devising ways to combat these infections have been hindered by an inability to genetically manipulate clini
Published: 2019

17. Reconstruction of the Genomes of Drug-Resistant Pathogens for Outbreak Investigation through Metagenomic Sequencing

Author: Gales, AC, Mu, A, Kwong, JC, Isles, NS, da Silva, AG, Schultz, MB, Ballard, SA, Lane, CR, Carter, GP, Williamson, DA, Seemann, T, Stinear, TP, Howden, BP, Gales, AC, Mu, A, Kwong, JC, Isles, NS, da Silva, AG, Schultz, MB, Ballard, SA, Lane, CR, Carter, GP, Williamson, DA, Seemann, T, Stinear, TP, and Howden, BP
Abstract: Culture-independent methods that target genome fragments have shown promise in identifying certain pathogens, but the holy grail of comprehensive pathogen genome detection from microbiologically complex samples for subsequent forensic analyses remains a challenge. In the context of an investigation of a nosocomial outbreak, we used shotgun metagenomic sequencing of a human fecal sample and a neural network algorithm based on tetranucleotide frequency profiling to reconstruct microbial genomes and tested the same approach using rectal swabs from a second patient. The approach rapidly and readily detected the genome of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae in the patient fecal specimen and in the rectal swab sample, achieving a level of strain resolution that was sufficient for confident transmission inference during a highly clonal outbreak. The analysis also detected previously unrecognized colonization of the patient by vancomycin-resistant Enterococcus faecium, another multidrug-resistant bacterium.IMPORTANCE The study results reported here perfectly demonstrate the power and promise of clinical metagenomics to recover genome sequences of important drug-resistant bacteria and to rapidly provide rich data that inform outbreak investigations and treatment decisions, independently of the need to culture the organisms.
Published: 2019

18. Genomics for Molecular Epidemiology and Detecting Transmission of Carbapenemase-Producing Enterobacterales in Victoria, Australia, 2012 to 2016

Author: Diekema, DJ, Sherry, NL, Lane, CR, Kwong, JC, Schultz, M, Sait, M, Stevens, K, Ballard, S, da Silva, AG, Seemann, T, Gorrie, CL, Stinear, TP, Williamson, DA, Brett, J, van Diemen, A, Easton, M, Howden, BP, Diekema, DJ, Sherry, NL, Lane, CR, Kwong, JC, Schultz, M, Sait, M, Stevens, K, Ballard, S, da Silva, AG, Seemann, T, Gorrie, CL, Stinear, TP, Williamson, DA, Brett, J, van Diemen, A, Easton, M, and Howden, BP
Abstract: Carbapenemase-producing Enterobacterales (CPE) are being increasingly reported in Australia, and integrated clinical and genomic surveillance is critical to effectively manage this threat. We sought to systematically characterize CPE in Victoria, Australia, from 2012 to 2016. Suspected CPE were referred to the state public health laboratory in Victoria, Australia, from 2012 to 2016 and examined using phenotypic, multiplex PCR and whole-genome sequencing (WGS) methods and compared with epidemiological metadata. Carbapenemase genes were detected in 361 isolates from 291 patients (30.8% of suspected CPE isolates), mostly from urine (42.1%) or screening samples (34.8%). IMP-4 (28.0% of patients), KPC-2 (25.3%), NDM (24.1%), and OXA carbapenemases (22.0%) were most common. Klebsiella pneumoniae (48.8% of patients) and Escherichia coli (26.1%) were the dominant species. Carbapenemase-inactivation method (CIM) testing reliably detected carbapenemase-positive isolates (100% sensitivity, 96.9% specificity), identifying an additional five CPE among 159 PCR-negative isolates (IMI and SME carbapenemases). When epidemiologic investigations were performed, all pairs of patients designated "highly likely" or "possible" local transmission had ≤23 pairwise single-nucleotide polymorphisms (SNPs) by genomic transmission analysis; conversely, all patient pairs designated "highly unlikely" local transmission had ≥26 pairwise SNPs. Using this proposed threshold, possible local transmission was identified involving a further 16 patients for whom epidemiologic data were unavailable. Systematic application of genomics has uncovered the emergence of polyclonal CPE as a significant threat in Australia, providing important insights to inform local public health guidelines and interventions. Using our workflow, pairwise SNP distances between CPE isolates of ≤23 SNPs suggest local transmission.
Published: 2019

19. Persistent low avian malaria in a tropical species despite high community prevalence

Author: Eastwood, JR, Peacock, L, Hall, ML, Roast, M, Murphy, SA, da Silva, AG, Peters, A, Eastwood, JR, Peacock, L, Hall, ML, Roast, M, Murphy, SA, da Silva, AG, and Peters, A
Abstract: Malarial and other haemosporidian parasites are widespread; however, their temporal dynamics are ill-understood. Longitudinal sampling of a threatened riparian bird revealed a consistently very low prevalence over 13 years (∼5%) despite infections persisting and prevalence increasing with age. In contrast, three key species within this tropical community were highly infected (∼20-75% prevalence) and these differences were stable. Although we found novel lineages and phylogenetic structure at the local level, there was little geographic structuring within Australasia. This study suggests that malarial parasite susceptibility is determined by host factors and that species can maintain low levels despite high community prevalence.
Published: 2019

20. Genomic investigation of Staphylococcus aureus recovered from Gambian women and newborns following an oral dose of intra-partum azithromycin

Author: Bojang, A, Baines, SL, Donovan, L, Guerillot, R, Stevens, K, Higgs, C, Bottomley, C, Secka, O, Schultz, MB, da Silva, AG, Seemann, T, Stinear, TP, Roca, A, Howden, BP, Bojang, A, Baines, SL, Donovan, L, Guerillot, R, Stevens, K, Higgs, C, Bottomley, C, Secka, O, Schultz, MB, da Silva, AG, Seemann, T, Stinear, TP, Roca, A, and Howden, BP
Abstract: BACKGROUND: Oral azithromycin given during labour reduces carriage of bacteria responsible for neonatal sepsis, including Staphylococcus aureus. However, there is concern that this may promote drug resistance. OBJECTIVES: Here, we combine genomic and epidemiological data on S. aureus isolated from mothers and babies in a randomized intra-partum azithromycin trial (PregnAnZI) to describe bacterial population dynamics and resistance mechanisms. METHODS: Participants from both arms of the trial, who carried S. aureus in day 3 and day 28 samples post-intervention, were included. Sixty-six S. aureus isolates (from 7 mothers and 10 babies) underwent comparative genome analyses and the data were then combined with epidemiological data. Trial registration (main trial): ClinicalTrials.gov Identifier NCT01800942. RESULTS: Seven S. aureus STs were identified, with ST5 dominant (n = 40, 61.0%), followed by ST15 (n = 11, 17.0%). ST5 predominated in the placebo arm (73.0% versus 49.0%, P = 0.039) and ST15 in the azithromycin arm (27.0% versus 6.0%, P = 0.022). In azithromycin-resistant isolates, msr(A) was the main macrolide resistance gene (n = 36, 80%). Ten study participants, from both trial arms, acquired azithromycin-resistant S. aureus after initially harbouring a susceptible isolate. In nine (90%) of these cases, the acquired clone was an msr(A)-containing ST5 S. aureus. Long-read sequencing demonstrated that in ST5, msr(A) was found on an MDR plasmid. CONCLUSIONS: Our data reveal in this Gambian population the presence of a dominant clone of S. aureus harbouring plasmid-encoded azithromycin resistance, which was acquired by participants in both arms of the study. Understanding these resistance dynamics is crucial to defining the public health drug resistance impacts of azithromycin prophylaxis given during labour in Africa.
Published: 2019

21. Emergence and divergence of major lineages of Shiga-toxin-producing Escherichia coli in Australia

Author: Ingle, DJ, da Silva, AG, Valcanis, M, Ballard, SA, Seemann, T, Jennison, A, Bastian, I, Wise, R, Kirk, MD, Howden, BP, Williamson, DA, Ingle, DJ, da Silva, AG, Valcanis, M, Ballard, SA, Seemann, T, Jennison, A, Bastian, I, Wise, R, Kirk, MD, Howden, BP, and Williamson, DA
Abstract: Shiga-toxin-producing Escherichia coli (STEC) infection is an important global cause of foodborne disease. To date however, genomics-based studies of STEC have been predominately focused upon STEC collected in the Northern Hemisphere. Here, we demonstrate the population structure of 485 STEC isolates in Australia, and show that several clonal groups (CGs) common to Australia were infrequently detected in a representative selection of contemporary STEC genomes from around the globe. Further, phylogenetic analysis demonstrated that lineage II of the global O157:H7 STEC was most prevalent in Australia, and was characterized by a frameshift mutation in flgF, resulting in the H-non-motile phenotype. Strong concordance between in silico and phenotypic serotyping was observed, along with concordance between in silico and conventional detection of stx genes. These data represent the most comprehensive STEC analysis from the Southern Hemisphere, and provide a framework for future national genomics-based surveillance of STEC in Australia.
Published: 2019

22. The changing landscape of VREfm in Victoria, Australia: a State-wide genomic snapshot

Author: Sarah L. Baines, Jason C Kwong, Benjamin P Howden, da Silva Ag, Dieter M. Bulach, Torsten Seemann, Susan A Ballard, Mark B. Schultz, Janet Strachan, Glen P. Carter, Timothy P. Stinear, and Robyn S Lee
Subjects: Genetics, 0303 health sciences, 030306 microbiology, Virulence, Single-nucleotide polymorphism, Context (language use), Biology, Sequence types, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, bacterial infections and mycoses, carbohydrates (lipids), 03 medical and health sciences, Plasmid, Genotype, Clade, 030304 developmental biology, Enterococcus faecium
Abstract: Vancomycin-resistantEnterococcus faecium(VREfm) represent a major source of nosocomial infection worldwide. In Australia, thevanBgenotype is dominant; however there has been a recent increase in the predominantly plasmid-encodedvanAgenotype, prompting investigation into the genomic epidemiology of VREfm in this context.Materials and MethodsA cross-sectional study of VREfm in Victoria, Australia (Nov.10th- Dec.9th, 2015). A total of 321 VREfm isolates (from 286 patients) were collected and whole-genome sequenced with Illumina NextSeq. Single nucleotide polymorphisms (SNPs) were used to assess relatedness. Multi-locus sequence types (STs), and genes associated with resistance and virulence were identified. ThevanA-harbouring plasmid from an isolate from each ST was assembled using long-read data.ResultsvanA-VREfm comprised 17.8% of isolates. ST203, ST80 and apstS(-) clade, ST1421, predominated (30.5%, 30.5% and 37.2% ofvanA-VREfm, respectively). MostvanB-VREfm were ST796 (77.7%).vanA-VREfm isolates were closely-related within hospitals vs. between them (core SNPs 10 [interquartile range 1-357] vs. 356 [179-416] respectively), suggesting discrete introductions ofvanA-VREfm, with subsequent intra-hospital transmission. In contrast,vanB-VREfm had similar core SNP distributions within vs. between hospitals, due to widespread dissemination of ST796. Overall,vanA-harbouring plasmids differed across STs, and with exception of ST78 and ST796, Tn1546transposons also varied.ConclusionsvanA-VREfm in Victoria is associated with multiple STs, and is not solely mediated by a single shared plasmid/Tn1546transposon; clonal transmission appears to play an important role, predominantly within, rather than between, hospitals. In contrast,vanB-VREfm appears to be well-established and widespread across Victorian healthcare institutions.
Published: 2018
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23. Translating genomics into practice for real-time surveillance and response to carbapenemase-producing Enterobacteriaceae: evidence from a complex multi-institutional KPC outbreak

Author: Kwong, JC, Lane, CR, Romanes, F, da Silva, AG, Easton, M, Cronin, K, Waters, MJ, Tomita, T, Stevens, K, Schultz, MB, Baines, SL, Sherry, NL, Carter, GP, Mu, A, Sait, M, Ballard, SA, Seemann, T, Stinear, TP, Howden, BP, Kwong, JC, Lane, CR, Romanes, F, da Silva, AG, Easton, M, Cronin, K, Waters, MJ, Tomita, T, Stevens, K, Schultz, MB, Baines, SL, Sherry, NL, Carter, GP, Mu, A, Sait, M, Ballard, SA, Seemann, T, Stinear, TP, and Howden, BP
Abstract: BACKGROUND: Until recently, Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae were rarely identified in Australia. Following an increase in the number of incident cases across the state of Victoria, we undertook a real-time combined genomic and epidemiological investigation. The scope of this study included identifying risk factors and routes of transmission, and investigating the utility of genomics to enhance traditional field epidemiology for informing management of established widespread outbreaks. METHODS: All KPC-producing Enterobacteriaceae isolates referred to the state reference laboratory from 2012 onwards were included. Whole-genome sequencing was performed in parallel with a detailed descriptive epidemiological investigation of each case, using Illumina sequencing on each isolate. This was complemented with PacBio long-read sequencing on selected isolates to establish high-quality reference sequences and interrogate characteristics of KPC-encoding plasmids. RESULTS: Initial investigations indicated that the outbreak was widespread, with 86 KPC-producing Enterobacteriaceae isolates (K. pneumoniae 92%) identified from 35 different locations across metropolitan and rural Victoria between 2012 and 2015. Initial combined analyses of the epidemiological and genomic data resolved the outbreak into distinct nosocomial transmission networks, and identified healthcare facilities at the epicentre of KPC transmission. New cases were assigned to transmission networks in real-time, allowing focussed infection control efforts. PacBio sequencing confirmed a secondary transmission network arising from inter-species plasmid transmission. Insights from Bayesian transmission inference and analyses of within-host diversity informed the development of state-wide public health and infection control guidelines, including interventions such as an intensive approach to screening contacts following new case detection to minimise unrecognised colonisation. CONC
Published: 2018

24. Comprehensive antibiotic-linked mutation assessment by resistance mutation sequencing (RM-seq)

Author: Guerillot, R, Li, L, Baines, S, Howden, B, Schultz, MB, Seemann, T, Monk, I, Pidot, SJ, Gao, W, Giulieri, S, da Silva, AG, D'Agata, A, Tomita, T, Peleg, AY, Stinear, TP, Howden, BP, Guerillot, R, Li, L, Baines, S, Howden, B, Schultz, MB, Seemann, T, Monk, I, Pidot, SJ, Gao, W, Giulieri, S, da Silva, AG, D'Agata, A, Tomita, T, Peleg, AY, Stinear, TP, and Howden, BP
Abstract: Mutation acquisition is a major mechanism of bacterial antibiotic resistance that remains insufficiently characterised. Here we present RM-seq, a new amplicon-based deep sequencing workflow based on a molecular barcoding technique adapted from Low Error Amplicon sequencing (LEA-seq). RM-seq allows detection and functional assessment of mutational resistance at high throughput from mixed bacterial populations. The sensitive detection of very low-frequency resistant sub-populations permits characterisation of antibiotic-linked mutational repertoires in vitro and detection of rare resistant populations during infections. Accurate quantification of resistance mutations enables phenotypic screening of mutations conferring pleiotropic phenotypes such as in vivo persistence, collateral sensitivity or cross-resistance. RM-seq will facilitate comprehensive detection, characterisation and surveillance of resistant bacterial populations ( https://github.com/rguerillot/RM-seq ).
Published: 2018

25. The changing landscape of vancomycin-resistant Enterococcus faecium in Australia: a population-level genomic study

Author: Lee, RS, da Silva, AG, Baines, SL, Strachan, J, Ballard, S, Carter, GP, Kwong, JC, Schultz, MB, Bulach, DM, Seemann, T, Stinear, TP, Howden, BP, Lee, RS, da Silva, AG, Baines, SL, Strachan, J, Ballard, S, Carter, GP, Kwong, JC, Schultz, MB, Bulach, DM, Seemann, T, Stinear, TP, and Howden, BP
Abstract: BACKGROUND: Vancomycin-resistant Enterococcus faecium (VREfm) represent a major source of nosocomial infection worldwide. In Australia, there has been a recent concerning increase in bacteraemia associated with the vanA genotype, prompting investigation into the genomic epidemiology of VREfm. METHODS: A population-level study of VREfm (10 November-9 December 2015) was conducted. A total of 321 VREfm isolates (from 286 patients) across Victoria State were collected and sequenced with Illumina NextSeq. SNPs were used to assess relatedness. STs and genes associated with resistance and virulence were identified. The vanA-harbouring plasmid from an isolate from each ST was assembled using long-read data. Illumina reads from remaining isolates were then mapped to these assemblies to identify their probable vanA-harbouring plasmid. RESULTS: vanA-VREfm comprised 17.8% of isolates. ST203, ST80 and a pstS(-) clade, ST1421, predominated (30.5%, 30.5% and 37.2%, respectively). Most vanB-VREfm were ST796 (77.7%). vanA-VREfm were more closely related within hospitals versus between them [core SNPs 10 (IQR 1-357) versus 356 (179-416), respectively], suggesting discrete introductions of vanA-VREfm, with subsequent intra-hospital transmission. In contrast, vanB-VREfm had similar core SNP distributions within versus between hospitals, due to widespread dissemination of ST796. Different vanA-harbouring plasmids were found across STs. With the exception of ST78 and ST796, Tn1546 transposons also varied. Phylogenetic analysis revealed Australian strains were often interspersed with those from other countries, suggesting ongoing cross-continental transmission. CONCLUSIONS: Emerging vanA-VREfm in Australia is polyclonal, indicating repeat introductions of vanA-VREfm into hospitals and subsequent dissemination. The close relationship to global strains reinforces the need for ongoing screening and control of VREfm in Australia and abroad.
Published: 2018

26. Convergent Evolution Driven by Rifampin Exacerbates the Global Burden of Drug-Resistant &ITStaphylococcus aureus&IT

Author: Fey, PD, Guerillot, R, da Silva, AG, Monk, I, Giulieri, S, Tomita, T, Alison, E, Porter, J, Pidot, S, Gao, W, Peleg, AY, Seemann, T, Stinear, TP, Howden, BP, Fey, PD, Guerillot, R, da Silva, AG, Monk, I, Giulieri, S, Tomita, T, Alison, E, Porter, J, Pidot, S, Gao, W, Peleg, AY, Seemann, T, Stinear, TP, and Howden, BP
Abstract: Mutations in the beta-subunit of bacterial RNA polymerase (RpoB) cause resistance to rifampin (Rifr), a critical antibiotic for treatment of multidrug-resistant Staphylococcus aureus. In vitro studies have shown that RpoB mutations confer decreased susceptibility to other antibiotics, but the clinical relevance is unknown. Here, by analyzing 7,099 S. aureus genomes, we demonstrate that the most prevalent RpoB mutations promote clinically relevant phenotypic plasticity resulting in the emergence of stable S. aureus lineages, associated with increased risk of therapeutic failure through generation of small-colony variants (SCVs) and coresistance to last-line antimicrobial agents. We found eight RpoB mutations that accounted for 93% (469/505) of the total number of Rifr mutations. The most frequently selected amino acid substitutions affecting residue 481 (H481N/Y) were associated with worldwide expansions of Rifr clones spanning decades. Recreating the H481N/Y mutations confirmed no impact on S. aureus growth, but the H481N mutation promoted the emergence of a subpopulation of stable Rifr SCVs with reduced susceptibility to vancomycin and daptomycin. Recreating the other frequent RpoB mutations showed similar impacts on resistance to these last-line agents. We found that 86% of all Rifr isolates in our global sample carried the mutations promoting cross-resistance to vancomycin and 52% to both vancomycin and daptomycin. As four of the most frequent RpoB mutations confer only low-level Rifr, equal to or below some international breakpoints, we recommend decreasing these breakpoints and reconsidering the appropriate use of rifampin to reduce the fixation and spread of these clinically deleterious mutations. IMPORTANCE Increasing antibiotic resistance in the major human pathogen Staphylococcus aureus is threatening the ability to treat patients with these infections. Recent laboratory studies suggest that mutations in the gene commonly associated with rifampin resistance
Published: 2018

27. Genomic Analysis of Multiresistant Staphylococcus capitis Associated with Neonatal Sepsis

Author: Carter, GP, Ussher, JE, Da Silva, AG, Baines, SL, Heffernan, H, Riley, T, Broadbent, R, van der Linden, A, Lee, J, Monk, IR, Stinear, TP, Howden, BP, Williamson, DA, Carter, GP, Ussher, JE, Da Silva, AG, Baines, SL, Heffernan, H, Riley, T, Broadbent, R, van der Linden, A, Lee, J, Monk, IR, Stinear, TP, Howden, BP, and Williamson, DA
Abstract: Coagulase-negative staphylococci (CoNS), such as Staphylococcus capitis, are major causes of bloodstream infections in neonatal intensive care units (NICUs). Recently, a distinct clone of S. capitis (designated S. capitis NRCS-A) has emerged as an important pathogen in NICUs internationally. Here, 122 S. capitis isolates from New Zealand (NZ) underwent whole-genome sequencing (WGS), and these data were supplemented with publicly available S. capitis sequence reads. Phylogenetic and comparative genomic analyses were performed, as were phenotypic assessments of antimicrobial resistance, biofilm formation, and plasmid segregational stability on representative isolates. A distinct lineage of S. capitis was identified in NZ associated with neonates and the NICU environment. Isolates from this lineage produced increased levels of biofilm, displayed higher levels of tolerance to chlorhexidine, and were multidrug resistant. Although similar to globally circulating NICU-associated S. capitis strains at a core-genome level, NZ NICU S. capitis isolates carried a novel stably maintained multidrug-resistant plasmid that was not present in non-NICU isolates. Neonatal blood culture isolates were indistinguishable from environmental S. capitis isolates found on fomites, such as stethoscopes and neonatal incubators, but were generally distinct from those isolates carried by NICU staff. This work implicates the NICU environment as a potential reservoir for neonatal sepsis caused by S. capitis and highlights the capacity of genomics-based tracking and surveillance to inform future hospital infection control practices aimed at containing the spread of this important neonatal pathogen.
Published: 2018

28. Genomic epidemiology and antimicrobial resistance of Neisseria gonorrhoeae in New Zealand

Author: Lee, RS, Seemann, T, Heffernan, H, Kwong, JC, da Silva, AG, Carter, GP, Woodhouse, R, Dyet, KH, Bulach, DM, Stinear, TP, Howden, BP, Williamson, DA, Lee, RS, Seemann, T, Heffernan, H, Kwong, JC, da Silva, AG, Carter, GP, Woodhouse, R, Dyet, KH, Bulach, DM, Stinear, TP, Howden, BP, and Williamson, DA
Abstract: BACKGROUND: Antimicrobial-resistant Neisseria gonorrhoeae is a major threat to public health. No studies to date have examined the genomic epidemiology of gonorrhoea in the Western Pacific Region, where the incidence of gonorrhoea is particularly high. METHODS: A population-level study of N. gonorrhoeae in New Zealand (October 2014 to May 2015). Comprehensive susceptibility testing and WGS data were obtained for 398 isolates. Relatedness was inferred using phylogenetic trees, and pairwise core SNPs. Mutations and genes known to be associated with resistance were identified, and correlated with phenotype. RESULTS: Eleven clusters were identified. In six of these clusters, >25% of isolates were from females, while in eight of them, >15% of isolates were from females. Drug resistance was common; 98%, 32% and 68% of isolates were non-susceptible to penicillin, ciprofloxacin and tetracycline, respectively. Elevated MICs to extended-spectrum cephalosporins (ESCs) were observed in 3.5% of isolates (cefixime MICs ≥ 0.12 mg/L, ceftriaxone MICs ≥ 0.06 mg/L). Only nine isolates had penA XXXIV genotypes, three of which had decreased susceptibility to ESCs (MIC = 0.12 mg/L). Azithromycin non-susceptibility was identified in 43 isolates (10.8%); two of these isolates had 23S mutations (C2611T, 4/4 alleles), while all had mutations in mtrR or its promoter. CONCLUSIONS: The high proportion of females in clusters suggests transmission is not exclusively among MSM in New Zealand; re-assessment of risk factors for transmission may be warranted in this context. As elevated MICs of ESCs and/or azithromycin were found in closely related strains, targeted public health interventions to halt transmission are urgently needed.
Published: 2018

29. Topical Antibiotic Use Coselects for the Carriage of Mobile Genetic Elements Conferring Resistance to Unrelated Antimicrobials in Staphylococcus aureus

Author: Carter, GP, Schultz, MB, Baines, SL, da Silva, AG, Heffernan, H, Tiong, A, Pham, PH, Monk, IR, Stinear, TP, Howden, BP, Williamson, DA, Carter, GP, Schultz, MB, Baines, SL, da Silva, AG, Heffernan, H, Tiong, A, Pham, PH, Monk, IR, Stinear, TP, Howden, BP, and Williamson, DA
Abstract: Topical antibiotics, such as mupirocin and fusidic acid, are commonly used in the prevention and treatment of skin infections, particularly those caused by staphylococci. However, the widespread use of these agents is associated with increased resistance to these agents, potentially limiting their efficacy. Of particular concern is the observation that resistance to topical antibiotics is often associated with multidrug resistance, suggesting that topical antibiotics may play a role in the emergence of multidrug-resistant (MDR) strains. New Zealand (NZ) has some of the highest globally recorded rates of topical antibiotic usage and resistance. Using a combination of Pacific Biosciences single-molecule real-time (SMRT) whole-genome sequencing, Illumina short-read sequencing, and Bayesian phylogenomic modeling on 118 new multilocus sequence type 1 (ST1) community Staphylococcus aureus isolates from New Zealand and 61 publically available international ST1 genome sequences, we demonstrate a strong correlation between the clinical introduction of topical antibiotics and the emergence of MDR ST1 S. aureus We also provide in vitro experimental evidence showing that exposure to topical antibiotics can lead to the rapid selection of MDR S. aureus isolates carrying plasmids that confer resistance to multiple unrelated antibiotics, from within a mixed population of competitor strains. These findings have important implications regarding the impact of the indiscriminate use of topical antibiotics.
Published: 2018

30. Augmented muscle vasodilatory responses in obese children with Glu27 ß2 adrenoceptor polymorphism.

Author: Da Silva AG, Ribeiro MM, Trombetta IC, Nicolau C, Frazzatto E, Guazzelli I, Matos LNJ, Halpern A, Negrao CE, and Villares SMF
Abstract: This study examined forearm vasodilatation during mental challenge and exercise in 72 obese children (OC; age = 10 ± 0.1 years) homozygous with polymorphism in the allele 27 of the [beta]2-adrenoceptors: Gln27 (n = 61) and Glu27 (n = 11). Forearm blood flow was recorded during 3 min of each using the Stroop color-word test (MS) and handgrip isometric exercise. Baseline hemodynamic and vascular measurements were similar. During the MS, peak forearm vascular conductance was significantly greater in group Glu27 ([Delta] = 0.35 ± 0.4 vs. 0.12 ± 0.1 units, respectively, p = .042). Similar results were found during exercise ([Delta] = 0.64 ± 0.1 vs. 0.13 ± 0.1 units, respectively, p = .035). Glu27 OC increased muscle vasodilatory responsiveness upon the MS and exercise. [ABSTRACT FROM AUTHOR]
Published: 2008
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31. A Supervised Statistical Learning Approach for Accurate Legionella pneumophila Source Attribution during Outbreaks

Author: Schaffner, DW, Buultjens, AH, Chua, KYL, Baines, SL, Kwong, J, Gao, W, Cutcher, Z, Adcock, S, Ballard, S, Schultz, MB, Tomita, T, Subasinghe, N, Carter, GP, Pidot, SJ, Franklin, L, Seemann, T, Da Silva, AG, Howden, BP, Stinear, TP, Schaffner, DW, Buultjens, AH, Chua, KYL, Baines, SL, Kwong, J, Gao, W, Cutcher, Z, Adcock, S, Ballard, S, Schultz, MB, Tomita, T, Subasinghe, N, Carter, GP, Pidot, SJ, Franklin, L, Seemann, T, Da Silva, AG, Howden, BP, and Stinear, TP
Abstract: Public health agencies are increasingly relying on genomics during Legionnaires' disease investigations. However, the causative bacterium (Legionella pneumophila) has an unusual population structure, with extreme temporal and spatial genome sequence conservation. Furthermore, Legionnaires' disease outbreaks can be caused by multiple L. pneumophila genotypes in a single source. These factors can confound cluster identification using standard phylogenomic methods. Here, we show that a statistical learning approach based on L. pneumophila core genome single nucleotide polymorphism (SNP) comparisons eliminates ambiguity for defining outbreak clusters and accurately predicts exposure sources for clinical cases. We illustrate the performance of our method by genome comparisons of 234 L. pneumophila isolates obtained from patients and cooling towers in Melbourne, Australia, between 1994 and 2014. This collection included one of the largest reported Legionnaires' disease outbreaks, which involved 125 cases at an aquarium. Using only sequence data from L. pneumophila cooling tower isolates and including all core genome variation, we built a multivariate model using discriminant analysis of principal components (DAPC) to find cooling tower-specific genomic signatures and then used it to predict the origin of clinical isolates. Model assignments were 93% congruent with epidemiological data, including the aquarium Legionnaires' disease outbreak and three other unrelated outbreak investigations. We applied the same approach to a recently described investigation of Legionnaires' disease within a UK hospital and observed a model predictive ability of 86%. We have developed a promising means to breach L. pneumophila genetic diversity extremes and provide objective source attribution data for outbreak investigations.IMPORTANCE Microbial outbreak investigations are moving to a paradigm where whole-genome sequencing and phylogenetic trees are used to support epidemiological investigat
Published: 2017

32. A phylogenomic framework for assessing the global emergence and evolution of clonal complex 398 methicillin-resistant Staphylococcus aureus

Author: da Silva, AG, Baines, SL, Carter, GP, Heffernan, H, French, NP, Ren, X, Seemann, T, Bulach, D, Kwong, J, Stinear, TP, Howden, BP, Williamson, DA, da Silva, AG, Baines, SL, Carter, GP, Heffernan, H, French, NP, Ren, X, Seemann, T, Bulach, D, Kwong, J, Stinear, TP, Howden, BP, and Williamson, DA
Abstract: Distinct clones of methicillin-resistant Staphylococcus aureus (MRSA) have emerged as important causes of infection in individuals who have exposure to livestock (livestock-associated MRSA; LA-MRSA). Clonal complex 398 (CC398) is the most prevalent LA-MRSA clone, and has been reported from several geographical settings, including Europe, the Americas and Asia. To understand the factors contributing to the global dissemination of this clone, we analysed CC398 MRSA isolates from New Zealand (NZ), a geographically isolated country with an economy strongly dependent on livestock farming. We supplemented the NZ CC398 MRSA collection with global datasets of CC398 MRSA and CC398 methicillin-susceptible S. aureus. Here, we demonstrate multiple sporadic incursions of CC398 MRSA into NZ, as well as recent importation and spread of a swine-associated clade related to the European LA-MRSA lineage. Within a larger global phylogenomic framework, Bayesian modelling suggested that this NZ clade emerged in the late 2000s, with a probable origin in swine from Western Europe. Elucidating the factors responsible for the incursion and spread of LA-MRSA in geographically distant regions, such as NZ, provides important insights into global pathways of S. aureus transmission, and will inform strategies to control importation and spread.
Published: 2017

33. Scope for genetic rescue of an endangered subspecies though re-establishing natural gene flow with another subspecies

Author: Harrisson, KA, Pavlova, A, da Silva, AG, Rose, R, Bull, JK, Lancaster, ML, Murray, N, Quin, B, Menkhorst, P, Magrath, MJL, Sunnucks, P, Harrisson, KA, Pavlova, A, da Silva, AG, Rose, R, Bull, JK, Lancaster, ML, Murray, N, Quin, B, Menkhorst, P, Magrath, MJL, and Sunnucks, P
Abstract: Genetic diversity is positively linked to the viability and evolutionary potential of species but is often compromised in threatened taxa. Genetic rescue by gene flow from a more diverse or differentiated source population of the same species can be an effective strategy for alleviating inbreeding depression and boosting evolutionary potential. The helmeted honeyeater Lichenostomus melanops cassidix is a critically endangered subspecies of the common yellow-tufted honeyeater. Cassidix has declined to a single wild population of ~130 birds, despite being subject to intensive population management over recent decades. We assessed changes in microsatellite diversity in cassidix over the last four decades and used population viability analysis to explore whether genetic rescue through hybridization with the neighbouring Lichenostomus melanops gippslandicus subspecies constitutes a viable conservation strategy. The contemporary cassidix population is characterized by low genetic diversity and effective population size (N(e) < 50), suggesting it is vulnerable to inbreeding depression and will have limited capacity to evolve to changing environments. We find that gene flow from gippslandicus to cassidix has declined substantially relative to pre-1990 levels and argue that natural levels of gene flow between the two subspecies should be restored. Allowing gene flow (~4 migrants per generation) from gippslandicus into cassidix (i.e. genetic rescue), in combination with continued annual release of captive-bred cassidix (i.e. demographic rescue), should lead to positive demographic and genetic outcomes. Although we consider the risk of outbreeding depression to be low, we recommend that genetic rescue be managed within the context of the captive breeding programme, with monitoring of outcomes.
Published: 2016

34. Genomic Insights into a Sustained National Outbreak of Yersinia pseudotuberculosis

Author: Williamson, DA, Baines, SL, Carter, GP, da silva, AG, Ren, X, Sherwood, J, Dufour, M, Schultz, MB, French, NP, Seemann, T, Stinear, TP, Howden, BP, Williamson, DA, Baines, SL, Carter, GP, da silva, AG, Ren, X, Sherwood, J, Dufour, M, Schultz, MB, French, NP, Seemann, T, Stinear, TP, and Howden, BP
Abstract: In 2014, a sustained outbreak of yersiniosis due to Yersinia pseudotuberculosis occurred across all major cities in New Zealand (NZ), with a total of 220 laboratory-confirmed cases, representing one of the largest ever reported outbreaks of Y. pseudotuberculosis. Here, we performed whole genome sequencing of outbreak-associated isolates to produce the largest population analysis to date of Y. pseudotuberculosis, giving us unprecedented capacity to understand the emergence and evolution of the outbreak clone. Multivariate analysis incorporating our genomic and clinical epidemiological data strongly suggested a single point-source contamination of the food chain, with subsequent nationwide distribution of contaminated produce. We additionally uncovered significant diversity in key determinants of virulence, which we speculate may help explain the high morbidity linked to this outbreak.
Published: 2016

35. NGMASTER: in silico multi-antigen sequence typing for Neisseria gonorrhoeae

Author: Kwong, JC, da Silva, AG, Dyet, K, Williamson, DA, Stinear, TP, Howden, BP, Seemann, T, Kwong, JC, da Silva, AG, Dyet, K, Williamson, DA, Stinear, TP, Howden, BP, and Seemann, T
Abstract: Whole-genome sequencing (WGS) provides the highest resolution analysis for comparison of bacterial isolates in public health microbiology. However, although increasingly being used routinely for some pathogens such as Listeria monocytogenes and Salmonella enterica, the use of WGS is still limited for other organisms, such as Neisseria gonorrhoeae. Multi-antigen sequence typing (NG-MAST) is the most widely performed typing method for epidemiological surveillance of gonorrhoea. Here, we present NGMASTER, a command-line software tool for performing in silico NG-MAST on assembled genome data. NGMASTER rapidly and accurately determined the NG-MAST of 630 assembled genomes, facilitating comparisons between WGS and previously published gonorrhoea epidemiological studies. The source code and user documentation are available at https://github.com/MDU-PHL/ngmaster.
Published: 2016

36. Kinship and Social Behavior of Lowland Tapirs (Tapirus terrestris) in a Central Amazon Landscape

Author: Singh, N, Pinho, GM, da Silva, AG, Hrbek, T, Venticinque, EM, Farias, IP, Singh, N, Pinho, GM, da Silva, AG, Hrbek, T, Venticinque, EM, and Farias, IP
Abstract: We tested the hypothesis that tapirs tolerate individuals from adjacent and overlapping home ranges if they are related. We obtained genetic data from fecal samples collected in the Balbina reservoir landscape, central Amazon. Samples were genotyped at 14 microsatellite loci, of which five produced high quality informative genotypes. Based on an analysis of 32 individuals, we inferred a single panmictic population with high levels of heterozygosity. Kinship analysis identified 10 pairs of full siblings or parent-offspring, 10 pairs of half siblings and 25 unrelated pairs. In 10 cases, the related individuals were situated on opposite margins of the reservoir, suggesting that tapirs are capable of crossing the main river, even after damming. The polygamous model was the most likely mating system for Tapirus terrestris. Moran's I index of allele sharing between pairs of individuals geographically close (<3 km) was similar to that observed between individual pairs at larger distances (>3 km). Confirming this result, the related individuals were not geographically closer than unrelated ones (W = 188.5; p = 0.339). Thus, we found no evidence of a preference for being close to relatives and observed a tendency for dispersal. The small importance of relatedness in determining spatial distribution of individuals is unusual in mammals, but not unheard of. Finally, non-invasive sampling allowed efficient access to the genetic data, despite the warm and humid climate of the Amazon, which accelerates DNA degradation.
Published: 2014

37. Perfil de isotipos de imunoglobulinas e subclasses de IgG na leishmaniose tegumentar americana

Author: Afonso-Cardoso, de Souza Ma, Favoreto Sj, da Silva Ag, and Marcelo Simão Ferreira
Subjects: Microbiology (medical), lcsh:Arctic medicine. Tropical medicine, Tegumentary leishmaniasis, lcsh:RC955-962, High avidity, Immunoglobulin Isotypes, RC955-962, Leishmaniose tegumentar americana, Immunoglobulin E, Subclass, Arctic medicine. Tropical medicine, Medicine, Avidity, Avidez, biology, business.industry, Imunoglobulinas, Subclasses de IgG, Leishmania, biology.organism_classification, Infectious Diseases, Immunology, biology.protein, Parasitology, Antibody, business
Abstract: O presente trabalho avaliou o perfil de anticorpos em amostras de soro de 37 pacientes com diagnóstico clínico confirmado ou compatível com leishmaniose tegumentar americana atendidos no Hospital de Clínicas da Universidade Federal de Uberlândia, MG. Os perfis das classes de imunoglobulinas e subclasses de IgG foram analisados pelo teste ELISA indireto, utilizando-se antígeno solúvel de Leishmania (Leishmania) amazonensis. A avidez dos anticorpos foi determinada pelo tratamento com uréia a 6 M, após incubação dos soros com o antígeno. Observou-se que 97%, 94,6%, 57,5 e 21,5% das amostras testadas apresentaram anticorpos anti-Leishmania das classes IgE, IgG, IgA e IgM, respectivamente e, os perfis das subclasses de IgG demonstraram, IgG1>IgG3>IgG2>IgG4. Os anticorpos IgE anti-Leishmania de alta avidez corresponderam a 44,4%. Por outro lado, IgG e IgA anti-Leishmania foram em sua maioria (62,8 e 47,8%, respectivamente), de média avidez. A variação do perfil de isotipos, bem como a avidez das imunoglobulinas refletiu a complexidade da resposta imune humoral contra a leishmaniose tegumentar americana.
Published: 2005

38. Gene flow networks among American Aedes aegypti populations

Author: da Silva, AG, Cunha, ICL, Santos, WS, Luz, SLB, Ribolla, PEM, Abad-Franch, F, da Silva, AG, Cunha, ICL, Santos, WS, Luz, SLB, Ribolla, PEM, and Abad-Franch, F
Abstract: The mosquito Aedes aegypti, the dengue virus vector, has spread throughout the tropics in historical times. While this suggests man-mediated dispersal, estimating contemporary connectivity among populations has remained elusive. Here, we use a large mtDNA dataset and a Bayesian coalescent framework to test a set of hypotheses about gene flow among American Ae. aegypti populations. We assessed gene flow patterns at the continental and subregional (Amazon basin) scales. For the Americas, our data favor a stepping-stone model in which gene flow is higher among adjacent populations but in which, at the same time, North American and southeastern Brazilian populations are directly connected, likely via sea trade. Within Amazonia, the model with highest support suggests extensive gene flow among major cities; Manaus, located at the center of the subregional transport network, emerges as a potentially important connecting hub. Our results suggest substantial connectivity across Ae. aegypti populations in the Americas. As long-distance active dispersal has not been observed in this species, our data support man-mediated dispersal as a major determinant of the genetic structure of American Ae. aegypti populations. The inferred topology of interpopulation connectivity can inform network models of Ae. aegypti and dengue spread.
Published: 2012

39. Population history, phylogeography, and conservation genetics of the last Neotropical mega-herbivore, the lowland tapir (Tapirus terrestris)

Author: de Thoisy, B, da Silva, AG, Ruiz-Garcia, M, Tapia, A, Ramirez, O, Arana, M, Quse, V, Paz-y-Mino, C, Tobler, M, Pedraza, C, Lavergne, A, de Thoisy, B, da Silva, AG, Ruiz-Garcia, M, Tapia, A, Ramirez, O, Arana, M, Quse, V, Paz-y-Mino, C, Tobler, M, Pedraza, C, and Lavergne, A
Abstract: BACKGROUND: Understanding the forces that shaped Neotropical diversity is central issue to explain tropical biodiversity and inform conservation action; yet few studies have examined large, widespread species. Lowland tapir (Tapirus terrrestris, Perissodactyla, Tapiridae) is the largest Neotropical herbivore whose ancestors arrived in South America during the Great American Biotic Interchange. A Pleistocene diversification is inferred for the genus Tapirus from the fossil record, but only two species survived the Pleistocene megafauna extinction. Here, we investigate the history of lowland tapir as revealed by variation at the mitochondrial gene Cytochrome b, compare it to the fossil data, and explore mechanisms that could have shaped the observed structure of current populations. RESULTS: Separate methodological approaches found mutually exclusive divergence times for lowland tapir, either in the late or in the early Pleistocene, although a late Pleistocene divergence is more in tune with the fossil record. Bayesian analysis favored mountain tapir (T. pinchaque) paraphyly in relation to lowland tapir over reciprocal monophyly, corroborating the inferences from the fossil data these species are sister taxa. A coalescent-based analysis rejected a null hypothesis of allopatric divergence, suggesting a complex history. Based on the geographic distribution of haplotypes we propose (i) a central role for western Amazonia in tapir diversification, with a key role of the ecological gradient along the transition between Andean subcloud forests and Amazon lowland forest, and (ii) that the Amazon river acted as an barrier to gene flow. Finally, the branching patterns and estimates based on nucleotide diversity indicate a population expansion after the Last Glacial Maximum. CONCLUSIONS: This study is the first examining lowland tapir phylogeography. Climatic events at the end of the Pleistocene, parapatric speciation, divergence along the Andean foothill, and role of the Amazo
Published: 2010

40. Evaluation of an extract of Brazilian arnica (Solidago chilensis Meyen, Asteraceae) in treating lumbago.

Author: da Silva AG, de Sousa CP, Koehler J, Fontana J, Christo AG, and Guedes-Bruni RR
Abstract: One of the Brazilian arnicas, Solidago chilensis Meyen, is a species of the family Asteraceae. This plant is known by this common name because it shares very similar organoleptic properties with the genus Arnica L., also within the family Asteraceae, that comprises approximately 30 European species of perennial, herbaceous plants. The effectiveness of a fluid extract of S. chilensis used externally for treating lumbago was examined in placebo-controlled double-blind clinical pharmacological studies. Two daily skin applications of a gel containing a 5% extract in glycol were administered for 15 days to ten volunteers in a placebo group and to an equal number in a test group. Statistical analyses of the results demonstrated a significant reduction in the perception of pain and a significant increase in the flexibility of patients in the test group as compared with those receiving only the placebo. [ABSTRACT FROM AUTHOR]
Published: 2010
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41. Humanized nursing care: difficulties found by nurses of a private hospital in São Paulo.

Author: da Silva AG, de Souza TTR, and Marcelino K
Published: 2008

42. Aspectos ultra-estruturais da doença de Parkinson

Author: da Silva Ag, de Mattos Jp, Fonseca Me, and Alexandre Alencar
Subjects: business.industry, Disease, Anatomy, Mitochondrion, lcsh:RC321-571, medicine.anatomical_structure, Neurology, Interstitial space, Cytoplasm, Neuropil, Ultrastructure, Medicine, Neurology (clinical), business, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
Abstract: A análise de cinco encéfalos humanos, quatro de pacientes parkinsonianos e um de controle, pela microscopia eletrônica de transmissão, evidenciou as seguintes mais freqüentes alterações: empobrecimento de fibras nervosas, grande aumento do espaço intersticial, desintegração do neurópilo e tumefação e degeneração das mitocôndrias. Com exceção das alterações mitocondriais, as demais ocorreram em todos os encéfalos dos parkinsonianos, fato não observado no caso controle, o que torna difícil atribuí-las à fixação. Traduzem, em última análise, a perda neuronal crônica. Houve, também, presença de depósitos amorfos no interior das mitocôndrias, dos axônios, do citoplasma e do espaço intersticial. Brains from four parkinsonian patients and one control patient were analysed by electron microscopy. The most consistent abnormal findings were nerve fibers rarefaction, great interstitial space enlargement, neuropil disruption, mitochondrial tumefaction and degenerative changes. These findings occurred regularly in the brain of parkinsonian patients. Furthermore, except for mitochondrial changes, they were distinctively absent in the control patient, and therefore cannot be attributed to technical problems. Contrarywise, they clearly reflect chronic neuronal loss. Also noteworthy was the demonstrative of deposits of amorphous substance into mitochondria, axons, cytoplasm and into the interstitial space.
Published: 1989

43. Demographic characteristics and clinical-radiological correlation in patients with indications for Total Knee Arthroplasty: A cross-sectional study.

Author: Munhoz DU, Moreira da Silva AG, Giglio PN, Helito CP, Gobbi RG, and Tirico LEP
Subjects: Humans, Cross-Sectional Studies, Female, Male, Middle Aged, Aged, Quality of Life, Surveys and Questionnaires, Knee Joint diagnostic imaging, Knee Joint surgery, Severity of Illness Index, Aged, 80 and over, Arthroplasty, Replacement, Knee methods, Osteoarthritis, Knee surgery, Osteoarthritis, Knee diagnostic imaging, Radiography
Abstract: Objective: The objective of this study is to correlate clinical symptoms and functionality, using the KOOS (Knee Injury and Osteoarthritis Outcome Score) and KSS (Knee Society Score System) scores, with the radiographic changes, using the Kellgren-Lawrence classification, in patients with knee osteoarthritis and indications for Total Knee Arthroplasty (TKA)., Methods: 120 patients (189 knees) with gonarthrosis and indications for TKA were included in the study. Demographic questionnaires were applied, and clinical and functional assessment was carried out using the KOOS and KSS scores. Knee radiographs were taken and graded according to Kellgren-Lawrence. The clinical scores were compared with the radiographic classification to establish a correlation between these two measurements. Statistical analysis was performed using the τ-Kendall correlation test., Results: Weak and inversely proportional correlations were found between the clinical scores and the radiographic classification. Among clinical scores evaluated, KSS showed the highest correlation with Kellgren-Lawrence classification (τ = -0.356; p < 0.001), followed by KOOS-quality of life (τ = -0.176; p = 0.004), KOOS-total score (τ = -0.166; p = 0.004), KOOS-function in daily living (τ = -0.160; p = 0.005) and KOOS-symptoms (τ = -0.159; p = 0.006). KOOS-pain (τ = -0.149; p = 0.01) and KOOS-sport and recreation function (τ = -0.142; p = 0.025) scores had the weakest correlations., Conclusion: There is a weak correlation between the clinical-functional scores of TKA candidates and their radiographic classification by Kellgren-Lawrence. Among clinical scores evaluated, KSS had the strongest negative correlation with the radiographic classification., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)
Published: 2024
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44. Erratum to: "Cross-cultural adaptation, validity, and reliability of the Child and Adolescent Behavior Inventory (CABI) for use in Brazil" (Jornal de Pediatria 99 (2023) 413-422).

Author: Costa DS, Cianchetti C, Dewey D, Alvim-Soares AM, Kestelman I, da Silva AG, Malloy-Diniz LF, Miranda DM, and de Paula JJ
Published: 2024
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45. Effect of Preoperative Anterolateral Ligament Injury on Outcomes After Isolated Acute ACL Reconstruction With Hamstring Graft: A Prospective Study With Minimum 5-Year Follow-up.

Author: Sobrado MF, Moreira da Silva AG, Helito PVP, and Helito CP
Subjects: Humans, Prospective Studies, Adult, Male, Female, Follow-Up Studies, Young Adult, Treatment Outcome, Adolescent, Hamstring Tendons transplantation, Anterior Cruciate Ligament Reconstruction methods, Anterior Cruciate Ligament Injuries surgery, Magnetic Resonance Imaging
Abstract: Background: The potential influence of a preoperative anterolateral ligament (ALL) lesion seen on magnetic resonance imaging (MRI) on the mid- and long-term surgical outcomes of anterior cruciate ligament (ACL) reconstruction is still controversial., Purpose: To evaluate the clinical outcomes and failure rate of isolated ACL reconstruction at a minimum 5-year follow-up in patients with and without ALL injury diagnosed preoperatively using MRI., Study Design: Cohort study; Level of evidence, 2., Methods: A prospective cohort of patients with acute ACL injury was divided into 2 groups based on the presence (ALL injury group) or absence (control group) of ALL injury on preoperative MRI. This is a longer-term follow-up study of a previously published study that had a minimum 2-year follow-up. Both groups underwent anatomic isolated reconstruction of the ACL. The Lysholm and subjective International Knee Documentation Committee scores, KT-1000 arthrometer and pivot-shift tests, reconstruction failure rate, incidence of contralateral ACL injury, presence of associated meniscal injury, and presence of knee hyperextension were evaluated. The evaluation at the 5-year follow-up was also compared with the same patient's evaluation at 2 years of follow-up., Results: A total of 156 patients were evaluated. No significant differences were found between the groups in the preoperative evaluation. In the postoperative evaluation, patients in the ALL injury group had a higher reconstruction failure rate (14.3% vs 4.6% for the control group; P = .049) and worse clinical outcomes according to the Lysholm scores (85.0 ± 10.3 vs 92.3 ± 6.6; P < .00001). Although the pivot-shift test results were similar, anteroposterior translation using the KT-1000 arthrometer revealed worse results for the ALL injury group (2.8 ± 1.4 mm vs 1.9 ± 1.3 mm; P = .00018). Patients in the ALL injury group also had an increase in KT-1000 arthrometer values from 2 to 5 years (2.4 ± 1.6 vs 2.8 ± 1.4; P = .038). Patients in the control group had no differences in outcomes from 2 to 5 years of follow-up., Conclusion: Combined ACL and ALL injuries were associated with significantly less favorable outcomes than were isolated ACL injuries at a minimum follow-up of 5 years after isolated ACL reconstruction with hamstring autograft. Patients with concomitant ALL injury showed a higher failure rate and worse functional scores. Also, knee stability tended to slightly worsen from 2 to 5 years in cases of associated ALL injury., Competing Interests: The authors declared that they have no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.
Published: 2024
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46. Time trend analysis and impacts of the COVID-19 pandemic on mammography and Papanicolaou test coverage in Brazilian state capitals.

Author: da Silva AG, Silva TPRD, Vasconcelos NM, Santos FMD, Oliveira GC, and Malta DC
Subjects: Humans, Female, Brazil epidemiology, Adult, Middle Aged, Early Detection of Cancer statistics & numerical data, Early Detection of Cancer trends, Early Detection of Cancer methods, Aged, Young Adult, Vaginal Smears statistics & numerical data, Papanicolaou Test statistics & numerical data, COVID-19 epidemiology, Mammography statistics & numerical data, Mammography trends, Breast Neoplasms diagnosis, Breast Neoplasms epidemiology, Breast Neoplasms diagnostic imaging, Uterine Cervical Neoplasms diagnosis, Uterine Cervical Neoplasms epidemiology
Abstract: Background: Breast and cervical cancer are major public health issues globally. The reduction in incidence and mortality rates of these cancers is linked to effective prevention, early detection, and appropriate treatment measures. This study aims to analyze the temporal trends in the prevalence of mammography and Papanicolaou test coverage among women living in Brazilian state capitals between 2007 and 2023, and to compare the coverage of these tests before and during the Covid-19 pandemic., Methods: A time series study was conducted using data from the Surveillance System for Risk and Protective Factors for Chronic Diseases by Telephone Survey from 2007 to 2023. The variables analyzed included mammography and Papanicolaou test coverage according to education level, age group, race/skin color, regions, and Brazilian capitals. The Prais-Winsten regression model was used to analyze the time series, and Student's t-test was employed to compare the prevalence rates between 2019 and 2023., Results: Between 2007 and 2023, mammography coverage showed a stationary trend (71.1% in 2007 and 73.1% in 2023; p-value = 0.75) with a declining trend observed among women with 12 years or more of education (APC= -0.52% 95%CI -1.01%; -0.02%). Papanicolaou test coverage for all women aged between 25 and 64 exhibited a downward trend from 82% in 2007 to 76.8% in 2023 (APC= -0.45% 95%CI -0.76%; -0.13%). This decline was also noticed among those with 9 years or more of education; in the 25 to 44 age group; among women with white and mixed race; and in the Northeast, Central-West, Southeast, and South regions. When comparing coverage before and during Covid-19 pandemic, a reduction was noted for both tests., Conclusions: Over the years, there has been stability in mammography coverage and a decline in Papanicolaou test. The COVID-19 pandemic negatively impacted the number of these tests carried out among women, highlighting the importance of actions aimed at increasing coverage, especially among the most vulnerable groups., (© 2024. The Author(s).)
Published: 2024
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47. Recovery of Full Hyperextension After Anterior Cruciate Ligament Reconstruction Is Associated With Better Functional Outcomes but Greater Anterior Cruciate Ligament-Related Laxity After a Minimum 24-Month Follow-Up.

Author: Helito CP, Moreira da Silva AG, Gomes Gobbi R, and Pécora JR
Abstract: Purpose: To evaluate patients who had anterior cruciate ligament (ACL) reconstruction with preoperative hyperextension and compare physical examination (KT-1000 and pivot shift) and patient-reported outcome measures of patients who recovered the entire hyperextension with patients who did not., Methods: Patients aged 18 to 60 years with more than 5° of knee hyperextension who had anatomic ACL reconstruction with any graft from June 2013 to June 2021 and at least a 24-month follow-up were evaluated retrospectively. Hamstrings and patellar tendon grafts were fixed around 20° to 30° of flexion and in full extension, respectively. Patients who could recover hyperextension were compared with patients who did not. Preoperative, intraoperative, and postoperative data, including physical examination and patient-reported outcome measures, were evaluated., Results: Of the 225 patients evaluated, 48 (21.3%) did not recover hyperextension, and 177 recovered full range of motion. Patients who did not recover hyperextension had a larger graft diameter (8.7 ± 0.7 mm [confidence interval, 8.502-8.898 mm] vs 8.3 ± 0.7 mm [confidence interval, 8.197-8.403 mm]; P = .018). Regarding the postoperative subjective variables, patients who recovered hyperextension showed improvement on all scales (International Knee Documentation Committee, Lysholm, Forgotten Joint Score, and Global Perceived Effect) evaluated compared with patients who did not recover the range of motion. Patients who recovered hyperextension also showed more laxity on physical examination, measured by the KT-1000 (1.8 ± 0.8 vs 1.1 ± 1.0; P = .0006) and the pivot shift (62.1% [grade 0] and 37.9% [grade 1] vs 79.2% [grade 0] and 20.8% [grade 1]; P = .027)., Conclusions: Patients with knee hyperextension who regained range of motion after ACL reconstruction have worse knee laxity than patients who regained full extension but not hyperextension. However, patients who recover full range of motion showed higher scores on subjective function scales, including a greater number of patients who achieved patient acceptable symptom state for the International Knee Documentation Committee score., Level of Evidence: Level III, retrospective comparative therapeutic trial., (Copyright © 2024 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)
Published: 2024
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48. Rapid Molecular Diagnosis of Sporotrichosis Directly from Biological Samples from a Reference Center in Brazil.

Author: da Silva AG, de Matos AFC, de Sousa BR, Ferraz CE, Luiz RLF, Neves RP, Lima-Neto RG, and Oliveira MME
Abstract: The gold standard diagnosis of sporotrichosis is the isolation of Sporothrix sp. in culture media, but this is a time-consuming test that is susceptible to contamination and can be affected by the fungal load. Molecular methods such as nested PCR are gaining more ground in the management of several infections as they are tools for the rapid and accurate identification of microorganisms from pure cultures or directly from biological samples. This study aimed to apply a nested PCR molecular protocol for the rapid detection of Sporothrix spp. directly from clinical samples. Thirteen samples-six from skin biopsies, five from skin exudates, and two from conjunctival secretions-were obtained from patients diagnosed with sporotrichosis due to S. brasiliensis . Calmodulin gene sequencing identified all the isolates as S. brasiliensis . Nested PCR was able to detect all the Sporothrix sensu lato directly from clinical samples as well as the CBS 120339 reference strain. The nested PCR protocol stands out as a diagnostic alternative, as it allows the identification of Sporothrix spp. directly from clinical samples without the need for fungal isolation.
Published: 2024
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49. The Role of Psychiatry in Areas Affected by Natural Disasters.

Author: Weber CAT and da Silva AG
Abstract: Competing Interests: The authors report no conflicts of interest.
Published: 2024
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50. Availability of Electroconvulsive Therapy in Public Health Services in the Last Decade in Brazil.

Author: Mazucco JP, Smaira SI, da Silva AG, Brunoni AR, and Gallucci-Neto J
Subjects: Brazil, Humans, Retrospective Studies, Public Health, Health Services Accessibility, Surveys and Questionnaires, Electroconvulsive Therapy statistics & numerical data, Electroconvulsive Therapy trends
Abstract: Objective: To identify the current treatment options for electroconvulsive therapy (ECT) therapy in public services linked to the Unified Health System in Brazil and compare them with data published in 2012 based on their availability., Methods: In this retrospective observational study, we mapped institutions that perform ECT under public health services in Brazil. A questionnaire was administered to active and inactive service centers between August 2022 and June 2023., Results: We identified 16 institutions that performed ECT, including 12 linked to public universities and 4 with various links. In the last decade, 2 new public services that perform ECT in the country have emerged, whereas 4 services have ceased function. In 2022, the number of individuals treated with ECT per 100,000 population was 1.86, whereas the number of procedures performed per 100,000 people was 6.55., Conclusions: Although 2 new public ECT services have been identified, 4 have turned inactive. Most services are linked to public universities, and inactive service points to financial issues as the main factor in service interruption. Brazil has one of the lowest rates of individuals treated with ECT per 100,000 population compared with countries in North America and Europe. Thus, it is essential to raise awareness to improve ECT adoption rates and bring it out of the shadows in Brazil., Competing Interests: The authors have no conflicts of interest or financial disclosures to report., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
Published: 2024
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